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Bashirrohelleh MA, Bavarsad K, Khodadadi A, Shohan M, Asadirad A. Curcumin-enhanced stem cell exosomes: A novel approach to modulating neuroinflammation and improving cognitive function in a rat model of Alzheimer's disease. Eur J Pharmacol 2025; 999:177695. [PMID: 40315951 DOI: 10.1016/j.ejphar.2025.177695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 04/22/2025] [Accepted: 04/30/2025] [Indexed: 05/04/2025]
Abstract
The effect of Curcumin-enhanced stem cell exosomes on the learning and memory impairment induced by streptozotocin (STZ) and neuro-inflammation in rats was evaluated. An animal model of Alzheimer's disease (AD) was established by intracerebroventricular (ICV) injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). ICV STZ injections chronically reduce cerebral glucose uptake and produce other effects similar to pathological, molecular and behavioral features of AD. Numerous studies confirmed the anti-inflammatory and antioxidant properties of curcumin (a natural polyphenol) against free radicals, as well as its ability to inhibit the aggregation of proteins such as beta-amyloid and alpha-synuclein in disorders such as AD and Parkinson's disease. The use of extracellular vesicles has garnered a lot of interest in research studies because of the important roles that mesenchymal stem cell-derived exosomes play in permeability, retention, and drug delivery as well as their ability to reduce inflammatory cytokines (TNF-α, IL-1β, and IL-6). Furthermore, researches highlighted the positive effect of curcumin on neuronal differentiation of stem cells in vivo and in vitro. Since studies emphasized the ameliorating effect of curcumin-treated macrophage-exosomes on symptoms of Alzheimer's disease by inhibiting tau protein phosphorylation, we proposed that Curcumin-primed MSC exosomes may offer greater efficacy to alleviate AD compared to naïve MSC exosomes. In this study, we investigated the effect of curcumin in stimulating the anti-inflammatory potential of exosome-derived stem cells. We evaluated the effect of MSC-EXO and pre-treated MSC-EXO with curcumin (CUR-MSC-EXO) on inhibiting inflammation and memory and learning impairments. Following four intraperitoneal injections of MSC-EXO and CUR-MSC-EXO at a dosage of 30μg/body over 30 days, we found that MSC-EXO and CUR-MSC-EXO elevated anti-inflammatory cytokines (IL10, TGF-β) and reduced pro-inflammatory cytokines (IL1, TNF-α) in peripheral blood compared to the AD group. The elevated level of M2 anti-inflammatory microglia markers (Arg1, CD206) and decreased level expression of M1 pro-inflammatory markers (iNOS, CD86) indicated that the CUR-MSC-EXO effect was more significant in the polarization of microglia into the M2 phenotype in the rat hippocampus. Both treatment groups demonstrated improvements in memory and learning skills. The results of the passive avoidance learning in the rats with STZ-induced memory impairment, however, were better in the CUR-MSC-EXO. Additionally, after therapy, a decrease in degenerative neurons was seen. Therefore, using curcumin may stimulate the anti-inflammatory and neuroprotective potential of exosome-derived stem cells which could provide hope for Alzheimer's disease treatment in the future.
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Affiliation(s)
- Mohammad-Ali Bashirrohelleh
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur, University of Medical Sciences, Iran; Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Kowsar Bavarsad
- Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Khodadadi
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur, University of Medical Sciences, Iran; Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mojtaba Shohan
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur, University of Medical Sciences, Iran
| | - Ali Asadirad
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur, University of Medical Sciences, Iran; Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Almeida PSD, Barão K, Forones NM. SARCOPENIA AND GASTROINTESTINAL CANCER: NUTRITIONAL APPROACH FOCUSING ON CURCUMIN SUPPLEMENTATION. ARQUIVOS DE GASTROENTEROLOGIA 2025; 62:e24068. [PMID: 40197883 PMCID: PMC12043197 DOI: 10.1590/s0004-2803.24612024-068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 11/15/2024] [Indexed: 04/10/2025]
Abstract
BACKGROUND Sarcopenia is a syndrome characterized by decreased strength, quantity and/or quality of skeletal muscle mass. When associated with cancer, it correlates with poorer clinical outcomes. Cancers of the gastrointestinal tract, prevalent globally and in Brazil, are associated with a greater nutritional risk. Early detection and intervention for nutritional risks are critical in this population. Recent studies on turmeric/curcumin have demonstrated beneficial effects in cancer patients. Specifically, curcumin have shown promise in reducing muscle depletion, oxidative stress, and improving strength and fatigue, factors related to sarcopenia. This review aims to elucidate sarcopenia and sarcopenia secondary to cancer, emphasizing nutritional management and the role of curcumin supplementation. Effective cancer management, whether with or without sarcopenia, demands comprehensive public health strategies and multimodal interventions within healthcare institutions. Nutrition is pivotal across the cancer care journey, encompassing screening, guidance, and provision of nutrients that support maintaining or recovering body composition. Curcumin supplementation emerges as a potential adjuvant to the standard cancer treatment and sarcopenia management. Nevertheless, further clinical studies are warranted to substantiate these findings. BACKGROUND • Sarcopenia is a syndrome characterized by decreased strength, quantity and/or quality of skeletal muscle mass. BACKGROUND • Sarcopenia when associated with cancer, it correlates with poorer clinical outcomes. BACKGROUND • Curcumin has shown promise in reducing muscle depletion, oxidative stress, and improving strength and fatigue, factors related to sarcopenia. BACKGROUND • Curcumin supplementation emerges as a potential adjuvant to the standard cancer treatment and sarcopenia management.
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Affiliation(s)
- Pamela S de Almeida
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina, Divisão de Gastroenterologia, São Paulo, SP, Brasil
| | - Katia Barão
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina, Divisão de Gastroenterologia, São Paulo, SP, Brasil
| | - Nora M Forones
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina, Divisão de Gastroenterologia, São Paulo, SP, Brasil
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Hamilton AE, Waskiewicz N, Quinones GB, Capadona JR, Bentley M, Palermo EF, Gilbert RJ. Poly(curcumin- co-poly(ethylene glycol)) films provide neuroprotection following reactive oxygen species insult in vitro. J Neural Eng 2025; 22:10.1088/1741-2552/ada8df. [PMID: 39793199 PMCID: PMC11921994 DOI: 10.1088/1741-2552/ada8df] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 01/10/2025] [Indexed: 01/13/2025]
Abstract
Objective.Curcumin is an antioxidant and anti-inflammatory molecule that may provide neuroprotection following central nervous system injury. However, curcumin is hydrophobic, limiting its ability to be loaded and then released from biomaterials for neural applications. We previously developed polymers containing curcumin, and these polymers may be applied to neuronal devices or to neural injury to promote neuroprotection. Thus, our objective was to evaluate two curcumin polymers as potential neuroprotective materials for neural applications.Approach.For each curcumin polymer, we created three polymer solutions by varying the weight percentage of curcumin polymer in solvent. These solutions were subsequently coated onto glass coverslips, and the thickness of the polymer was assessed using profilometry. Polymer degradation and dissolution was assessed using brightfield microscopy, scanning electron microscopy, and gel permeation chromatography. The ability of the polymers to protect cortical neurons from free radical insult was assessed using anin vitrocortical culture model.Main results.The P50 curcumin polymer (containing greater poly(ethylene glycol) content than the P75 polymer), eroded readily in solution, with erosion dependent on the weight percentage of polymer in solvent. Unlike the P50 polymer, the P75 polymer did not undergo erosion. Since the P50 polymer underwent erosion, we expected that the P50 polymer would more readily protect cortical neurons from free radical insult. Unexpectedly, even though P75 films did not erode, P75 polymers protected neurons from free radical insult, suggesting that erosion is not necessary for these polymers to enable neuroprotection.Significance.This study is significant as it provides a framework to evaluate polymers for future neural applications. Additionally, we observed that some curcumin polymers do not require dissolution to enable neuroprotection. Future work will assess the ability of these materials to enable neuroprotection withinin vivomodels of neural injury.
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Affiliation(s)
- Adelle E. Hamilton
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, USA
- Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, USA
| | - Nikita Waskiewicz
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, USA
| | - Geraldine B. Quinones
- Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, USA
- Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, USA
| | - Jeffrey R. Capadona
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, USA
- Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, USA
| | - Marvin Bentley
- Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, USA
- Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, USA
| | - Edmund F. Palermo
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, USA
- Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, Troy, USA
| | - Ryan J. Gilbert
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, USA
- Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, USA
- Albany Stratton Veterans Affairs, Albany, USA
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Gareev I, Jiang J, Beylerli O, Beilerli A, Ilyasova T, Shumadalova A, Bai Y, Du W, Yang B. Adjuvant Anti-tumor Therapy with Polyphenolic Compounds: A Review. Curr Med Chem 2025; 32:1934-1967. [PMID: 40351076 DOI: 10.2174/0109298673284605240301035057] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 12/25/2023] [Accepted: 01/03/2024] [Indexed: 05/14/2025]
Abstract
The search for effective methods of treatment and prevention of oncological diseases, despite the successes achieved in recent decades, remains one of the most urgent issues in modern medicine. It is known that chemotherapy and radiation therapy are based on the induction of cell death by increasing the intracellular concentration of reactive oxygen species (ROS). To increase the effectiveness of chemo- and radiotherapy, inducing and increasing oxidative stress in tumor cells has been proposed. A new class of promising adjuvants in combination with anticancer therapy, which has already been shown to be effective in preclinical and clinical studies, includes natural and synthetic polyphenols. Polyphenolic compounds not only exhibit antitumor activity but also significantly reduce the resistance of tumor cells to chemo- and radiotherapy. However, almost all chemotherapeutic drugs and regimens of radiation treatment have a damaging toxic effect on normal tissues, which significantly affects the quality of life of patients, and treatment options for managing these side effects are limited. In this regard, some of the most promising agents for the management of toxic side effects are natural polyphenols. This study discusses the possible molecular mechanisms and prospects for the clinical use of natural and synthetic polyphenolic compounds in chemo- and radiotherapy. In addition, the protective role/effect of polyphenols on the effects of chemoand radiotherapy in tumor patients is discussed.
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Affiliation(s)
- Ilgiz Gareev
- Central Research Laboratory, Department of Pharmacology, Bashkir State Medical University, Republic of Bashkortostan, 3 Lenin Street, Ufa, 450008, Russia
| | - Jianhao Jiang
- The State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, 150067, China
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, 150081, P.R. China
| | - Ozal Beylerli
- Central Research Laboratory, Department of Pharmacology, Bashkir State Medical University, Republic of Bashkortostan, 3 Lenin Street, Ufa, 450008, Russia
| | - Aferin Beilerli
- Department of Obstetrics and Gynecology, Tyumen State Medical University, 54 Odesskaya Street, 625023, Tyumen, Russia
| | - Tatiana Ilyasova
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Republic of Bashkortostan, 3 Lenin Street, Ufa, 450008, Russia
| | - Alina Shumadalova
- Department of General Chemistry, Bashkir State Medical University, Republic of Bashkortostan, 3 Lenin Street, Ufa, 450008, Russia
| | - Yunlong Bai
- The State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, 150067, China
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, 150081, P.R. China
| | - Weijie Du
- The State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, 150067, China
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, 150081, P.R. China
| | - Baofeng Yang
- The State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, 150067, China
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, 150081, P.R. China
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Wei J, Wang X, Yu D, Tu Y, Yu Y. MicroRNA-mediated autophagy and drug resistance in cancer: mechanisms and therapeutic strategies. Discov Oncol 2024; 15:662. [PMID: 39549162 PMCID: PMC11569378 DOI: 10.1007/s12672-024-01525-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 11/04/2024] [Indexed: 11/18/2024] Open
Abstract
This paper provides an exhaustive overview of the intricate interplay between microRNAs (miRNAs) and autophagy in the context of human cancers, underscoring the pivotal role these non-coding RNAs play in modulating autophagic pathways and their implications for cancer development, progression, and resistance to therapy. MiRNAs, as critical regulators of gene expression post-transcription, influence various biological processes, including autophagy, a catabolic mechanism essential for cellular homeostasis, stress response, and survival. The review meticulously delineates the mechanisms through which miRNAs impact autophagy by targeting specific genes and signaling pathways, thereby affecting cancer cell proliferation, metastasis, and response to chemotherapy. It highlights several miRNAs with dual roles, acting either as oncogenes or tumor suppressors based on the cellular context and the specific autophagic pathways they regulate. The paper further explores the therapeutic potential of targeting miRNA-autophagy axis, offering insights into novel strategies for cancer treatment through modulation of this axis. Emphasizing the complexity of the miRNA-autophagy relationship, the review calls for more in-depth studies to unravel the nuanced regulatory networks between miRNAs and autophagy in cancer, which could pave the way for the development of innovative therapeutic interventions and diagnostic tools.
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Affiliation(s)
- Jinxing Wei
- Department of Neurosurgery, Brain Hospital Affiliated to Tongji University, No.2880, Qixin Road, Shanghai, China
| | - Xianghui Wang
- Department of Neurosurgery, Brain Hospital Affiliated to Tongji University, No.2880, Qixin Road, Shanghai, China
| | - Duo Yu
- Department of Biopharmaceutics School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China
| | - Yanyang Tu
- Research Center, The Huizhou Central People's Hospital, Guangdong Medical University, No. 41 Eling North Road, Huizhou, Guangdong, China.
| | - Yaoyu Yu
- Department of Neurosurgery, Brain Hospital Affiliated to Tongji University, No.2880, Qixin Road, Shanghai, China.
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Motamedzadeh A, Rahmati-Dehkordi F, Heydari H, Behnam M, Rashidi Noshabad FZ, Tamtaji Z, Taheri AT, Nabavizadeh F, Aschner M, Mirzaei H, Tamtaji OR. Therapeutic potential of Phycocyanin in gastrointestinal cancers and related disorders. Mol Biol Rep 2024; 51:741. [PMID: 38874869 DOI: 10.1007/s11033-024-09675-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 05/23/2024] [Indexed: 06/15/2024]
Abstract
Gastrointestinal cancer is the most fatal cancer worldwide. The etiology of gastrointestinal cancer has yet to be fully characterized. Alcohol consumption, obesity, tobacco, Helicobacter pylori and gastrointestinal disorders, including gastroesophageal reflux disease, gastric ulcer, colon polyps and non-alcoholic fatty liver disease are among the several risks factors for gastrointestinal cancers. Phycocyanin which is abundant in Spirulina. Phycocyanin, a member of phycobiliprotein family with intense blue color, is an anti-diabetic, neuroprotective, anti-oxidative, anti-inflammatory, and anticancer compound. Evidence exists supporting that phycocyanin has antitumor effects, exerting its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, cell-cycle arrest, migration and Wnt/β-catenin signaling. Phycocyanin has also been applied in treatment of several gastrointestinal disorders such as, gastric ulcer, ulcerative colitis and fatty liver that is known as a risk factor for progression to cancer. Herein, we summarize various cellular and molecular pathways that are affected by phycocyanin, its efficacy upon combined drug treatment, and the potential for nanotechnology in its gastrointestinal cancer therapy.
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Affiliation(s)
- Alireza Motamedzadeh
- Department of Internal Medicine, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Fatemeh Rahmati-Dehkordi
- Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hoora Heydari
- Student Research Committee, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohammad Behnam
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Zeinab Tamtaji
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Abdolkarim Talebi Taheri
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Nabavizadeh
- Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.
- Department of Physiology, School of Medicine, Tehran University of medical sciences, Tehran, Iran.
| | - Omid Reza Tamtaji
- Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
- Department of Physiology, School of Medicine, Tehran University of medical sciences, Tehran, Iran.
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Aloi E, Tone CM, Barberi RC, Ciuchi F, Bartucci R. Effects of curcumin in the interaction with cardiolipin-containg lipid monolayers and bilayers. Biophys Chem 2023; 301:107082. [PMID: 37544082 DOI: 10.1016/j.bpc.2023.107082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 07/21/2023] [Accepted: 07/30/2023] [Indexed: 08/08/2023]
Abstract
Curcumin, a plant polyphenol extracted from the Chinese herb turmeric, has gained widespread attention in recent years because of its multifunctional properties as antioxidant, antinflammatory, antimicrobial, and anticancer agent. Effects of the molecule on mitochondrial membranes properties have also been evidenced. In this work, the interaction of curcumin with models of mitochondrial membranes composed of dimyristoylphosphatidylcholine (DMPC) or mixtures of DMPC and 4 mol% tetramyristoylcardiolipin (TMCL) has been investigated by using biophysical techniques. Spectrophotometry and fluorescence allowed to determine the association constant and the binding energy of curcumin with pure DMPC and mixed DMPC/TMCL aqueous bilayers. The molecular organization of pure DMPC and cardiolipin-containing Langmuir monolayers at the air-water interface were investigated and the morphology of the monolayers transferred into mica substrates were characterized through atomic force microscopy (AFM). It is found that curcumin associates at the polar/apolar interface of the lipid bilayers and the binding is favored in the presence of cardiolipin. At 2 mol%, curcumin is well miscible with lipid monolayers, particularly with mixed DMPC/TMCL ones, where compact terraces formation characterized by a reduction of the surface roughness is observed in the AFM topographic images. At 10 mol%, curcumin perturbs the stability of DMPC monolayers and morphologically are evident terraces surrounded by cur aggregates. In the presence of TMCL, very few curcumin aggregates and larger compact terraces are observed. The overall results indicate that cardiolipin augments the incorporation of curcumin in model membranes highlighting the mutual interplay cardiolipin-curcumin in mitochondrial membranes.
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Affiliation(s)
- Erika Aloi
- Department of Physics, University of Calabria, 87036 Rende, Italy
| | - Caterina M Tone
- Department of Physics, University of Calabria, 87036 Rende, Italy; CNR Nanotec c/o Department of Physics, University of Calabria, 87036 Rende, Italy
| | - Riccardo C Barberi
- Department of Physics, University of Calabria, 87036 Rende, Italy; CNR Nanotec c/o Department of Physics, University of Calabria, 87036 Rende, Italy
| | - Federica Ciuchi
- CNR Nanotec c/o Department of Physics, University of Calabria, 87036 Rende, Italy.
| | - Rosa Bartucci
- Department of Chemistry and Chemical Technologies, University of Calabria, 87036 Rende, Italy.
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Czerwonka A, Kałafut J, Nees M. Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies. Cancers (Basel) 2023; 15:4563. [PMID: 37760535 PMCID: PMC10526229 DOI: 10.3390/cancers15184563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/03/2023] [Accepted: 09/07/2023] [Indexed: 09/29/2023] Open
Abstract
Notch signaling is responsible for conveying messages between cells through direct contact, playing a pivotal role in tissue development and homeostasis. The modulation of Notch-related processes, such as cell growth, differentiation, viability, and cell fate, offer opportunities to better understand and prevent disease progression, including cancer. Currently, research efforts are mainly focused on attempts to inhibit Notch signaling in tumors with strong oncogenic, gain-of-function (GoF) or hyperactivation of Notch signaling. The goal is to reduce the growth and proliferation of cancer cells, interfere with neo-angiogenesis, increase chemosensitivity, potentially target cancer stem cells, tumor dormancy, and invasion, and induce apoptosis. Attempts to pharmacologically enhance or restore disturbed Notch signaling for anticancer therapies are less frequent. However, in some cancer types, such as squamous cell carcinomas, preferentially, loss-of-function (LoF) mutations have been confirmed, and restoring but not blocking Notch functions may be beneficial for therapy. The modulation of Notch signaling can be performed at several key levels related to NOTCH receptor expression, translation, posttranslational (proteolytic) processing, glycosylation, transport, and activation. This further includes blocking the interaction with Notch-related nuclear DNA transcription. Examples of small-molecular chemical compounds, that modulate individual elements of Notch signaling at the mentioned levels, have been described in the recent literature.
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Affiliation(s)
- Arkadiusz Czerwonka
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland; (J.K.); (M.N.)
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Pouliquen DL, Trošelj KG, Anto RJ. Curcuminoids as Anticancer Drugs: Pleiotropic Effects, Potential for Metabolic Reprogramming and Prospects for the Future. Pharmaceutics 2023; 15:1612. [PMID: 37376060 DOI: 10.3390/pharmaceutics15061612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 05/21/2023] [Accepted: 05/24/2023] [Indexed: 06/29/2023] Open
Abstract
The number of published studies on curcuminoids in cancer research, including its lead molecule curcumin and synthetic analogs, has been increasing substantially during the past two decades. Insights on the diversity of inhibitory effects they have produced on a multitude of pathways involved in carcinogenesis and tumor progression have been provided. As this wealth of data was obtained in settings of various experimental and clinical data, this review first aimed at presenting a chronology of discoveries and an update on their complex in vivo effects. Secondly, there are many interesting questions linked to their pleiotropic effects. One of them, a growing research topic, relates to their ability to modulate metabolic reprogramming. This review will also cover the use of curcuminoids as chemosensitizing molecules that can be combined with several anticancer drugs to reverse the phenomenon of multidrug resistance. Finally, current investigations in these three complementary research fields raise several important questions that will be put among the prospects for the future research related to the importance of these molecules in cancer research.
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Affiliation(s)
- Daniel L Pouliquen
- Université d'Angers, Inserm, CNRS, Nantes Université, CRCI2NA, F-49000 Angers, France
| | - Koraljka Gall Trošelj
- Laboratory for Epigenomics, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia
| | - Ruby John Anto
- Molecular Bioassay Laboratory, Institute of Advanced Virology, Thiruvananthapuram 695317, India
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Lei N, Peng X, Hu M, Wan C, Yu X. Research on essential performance of oxidized chitosan-crosslinked acellular porcine aorta modified with bioactive SCPP/DOPA for esophageal scaffold with enhanced mechanical strength, biocompatibility and anti-inflammatory. Int J Biol Macromol 2023; 241:124522. [PMID: 37100332 DOI: 10.1016/j.ijbiomac.2023.124522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 04/06/2023] [Accepted: 04/15/2023] [Indexed: 04/28/2023]
Abstract
Acellular porcine aorta (APA) is an excellent candidate for an implanted scaffold but needs to be modified with appropriate cross-linking agent to increase its mechanical property and storage time in vitro as well as to give itself some bioactivities and eliminate its antigenicity for acting as a novel esophageal prosthesis. In this paper, a polysaccharide crosslinker (oxidized chitosan, OCS) was prepared by oxidizing chitosan using NaIO4 and further used to fix APA to prepare a novel esophageal prosthesis (scaffold). And then the surface modification with dopamine (DOPA) and strontium-doped calcium polyphosphate (SCPP) were performed one after another to prepare DOPA/OCS-APA and SCPP-DOPA/OCS-APA to improve the biocompatibility and inhibit inflammation of the scaffolds. The results showed that the OCS with a feeding ratio of 1.5:1.0 and a reaction time of 24 h had a suitable molecular weight and oxidation degree, almost no cytotoxicity and good cross-linking effect. Compared with glutaraldehyde (GA) and genipin (GP), OCS-fixed APA could provide a more suitable microenvironment for cell proliferation. The vital cross-linking characteristics and cytocompatibility of SCPP-DOPA/OCS-APA were evaluated. Results suggested that SCPP-DOPA/OCS-APA exhibited suitable mechanical properties, excellent resistance to enzymatic degradation/acid degradation, suitable hydrophilicity, and the ability to promote the proliferation of Human normal esophageal epithelial cells (HEECs) and inhibit inflammation in vitro. In vivo tests also confirmed that SCPP-DOPA/OCS-APA could diminish the immunological response to samples and had a positive impact on bioactivity and anti-inflammatory. In conclusion, SCPP-DOPA/OCS-APA could act as an effective, bioactive artificial esophageal scaffold and be expected to be used for clinical in the future.
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Affiliation(s)
- Ningning Lei
- College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, PR China
| | - Xu Peng
- Experimental and Research Animal Institute, Sichuan University, Chengdu 610065, PR China
| | - Mengyue Hu
- College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, PR China
| | - Chang Wan
- College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, PR China
| | - Xixun Yu
- College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, PR China.
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Curcumin Release from Biomaterials for Enhanced Tissue Regeneration Following Injury or Disease. Bioengineering (Basel) 2023; 10:bioengineering10020262. [PMID: 36829756 PMCID: PMC9951943 DOI: 10.3390/bioengineering10020262] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023] Open
Abstract
Curcumin, a bioactive phenol derived from turmeric, is an antioxidant, anti-inflammatory, and antibacterial molecule. Although curcumin exhibits beneficial effects in its innate form, it is highly hydrophobic, which leads to poor water solubility and, consequently, low bioavailability. The lack of bioavailability limits curcumin's effectiveness as a treatment and restricts its use in clinical applications. Furthermore, to achieve beneficial, clinically relevant results, high doses of curcumin are required for systemic administration. Many researchers have utilized biomaterial carriers, including electrospun fibers, nanoparticles, hydrogels, and composite scaffolds, to overcome curcumin's principle therapeutic limitation of low bioavailability. By using biomaterials to deliver curcumin directly to injury sites, researchers have harnessed the beneficial natural properties of curcumin while providing scaffolding to support tissue regeneration. This review will provide an in-depth overview of the literature that utilizes biomaterial delivery of curcumin for tissue regeneration in injury and disease models.
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12
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Regulatory Effects of Curcumin on Platelets: An Update and Future Directions. Biomedicines 2022; 10:biomedicines10123180. [PMID: 36551934 PMCID: PMC9775400 DOI: 10.3390/biomedicines10123180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/29/2022] [Accepted: 12/01/2022] [Indexed: 12/13/2022] Open
Abstract
The rhizomatous plant turmeric, which is frequently used as a spice and coloring ingredient, yields curcumin, a bioactive compound. Curcumin inhibits platelet activation and aggregation and improves platelet count. Platelets dysfunction results in several disorders, including inflammation, atherothrombosis, and thromboembolism. Several studies have proved the beneficial role of curcumin on platelets and hence proved it is an important candidate for the treatment of the aforementioned diseases. Moreover, curcumin is also frequently employed as an anti-inflammatory agent in conventional medicine. In arthritic patients, it has been shown to reduce the generation of pro-inflammatory eicosanoids and to reduce edema, morning stiffness, and other symptoms. Curcumin taken orally also reduced rats' acute inflammation brought on by carrageenan. Curcumin has also been proven to prevent atherosclerosis and platelet aggregation, as well as to reduce angiogenesis in adipose tissue. In the cerebral microcirculation, curcumin significantly lowered platelet and leukocyte adhesion. It largely modulated the endothelium to reduce platelet adhesion. Additionally, P-selectin expression and mice survival after cecal ligation and puncture were improved by curcumin, which also altered platelet and leukocyte adhesion and blood-brain barrier dysfunction. Through regulating many processes involved in platelet aggregation, curcuminoids collectively demonstrated detectable antiplatelet activity. Curcuminoids may therefore be able to prevent disorders linked to platelet activation as possible therapeutic agents. This review article proposes to highlight and discuss the regulatory effects of curcumin on platelets.
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13
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Bispo IMC, Granger HP, Almeida PP, Nishiyama PB, de Freitas LM. Systems biology and OMIC data integration to understand gastrointestinal cancers. World J Clin Oncol 2022; 13:762-778. [PMID: 36337313 PMCID: PMC9630993 DOI: 10.5306/wjco.v13.i10.762] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/22/2021] [Accepted: 10/02/2022] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) cancers are a set of diverse diseases affecting many parts/ organs. The five most frequent GI cancer types are esophageal, gastric cancer (GC), liver cancer, pancreatic cancer, and colorectal cancer (CRC); together, they give rise to 5 million new cases and cause the death of 3.5 million people annually. We provide information about molecular changes crucial to tumorigenesis and the behavior and prognosis. During the formation of cancer cells, the genomic changes are microsatellite instability with multiple chromosomal arrangements in GC and CRC. The genomically stable subtype is observed in GC and pancreatic cancer. Besides these genomic subtypes, CRC has epigenetic modification (hypermethylation) associated with a poor prognosis. The pathway information highlights the functions shared by GI cancers such as apoptosis; focal adhesion; and the p21-activated kinase, phosphoinositide 3-kinase/Akt, transforming growth factor beta, and Toll-like receptor signaling pathways. These pathways show survival, cell proliferation, and cell motility. In addition, the immune response and inflammation are also essential elements in the shared functions. We also retrieved information on protein-protein interaction from the STRING database, and found that proteins Akt1, catenin beta 1 (CTNNB1), E1A binding protein P300, tumor protein p53 (TP53), and TP53 binding protein 1 (TP53BP1) are central nodes in the network. The protein expression of these genes is associated with overall survival in some GI cancers. The low TP53BP1 expression in CRC, high EP300 expression in esophageal cancer, and increased expression of Akt1/TP53 or low CTNNB1 expression in GC are associated with a poor prognosis. The Kaplan Meier plotter database also confirmed the association between expression of the five central genes and GC survival rates. In conclusion, GI cancers are very diverse at the molecular level. However, the shared mutations and protein pathways might be used to understand better and reveal diagnostic/prognostic or drug targets.
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Affiliation(s)
- Iasmin Moreira Costa Bispo
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Henry Paul Granger
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Palloma Porto Almeida
- Division of Experimental and Translational Research, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, Brazil
| | - Patricia Belini Nishiyama
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Leandro Martins de Freitas
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
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14
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Ye X, Chen X, He R, Meng W, Chen W, Wang F, Meng X. Enhanced anti-breast cancer efficacy of co-delivery liposomes of docetaxel and curcumin. Front Pharmacol 2022; 13:969611. [PMID: 36324685 PMCID: PMC9618653 DOI: 10.3389/fphar.2022.969611] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 09/27/2022] [Indexed: 08/28/2023] Open
Abstract
The successful treatment of breast cancer is hampered by toxicity to normal cells, impaired drug accumulation at the tumor site, and multidrug resistance. We designed a novel multifunctional liposome, CUR-DTX-L, to co-deliver curcumin (CUR) and the chemotherapeutic drug docetaxel (DTX) for the treatment of breast cancer in order to address multidrug resistance (MDR) and the low efficacy of chemotherapy. The mean particle size, polydispersity index, zeta potential, and encapsulation efficiency of CUR-DTX-L were 208.53 ± 6.82 nm, 0.055 ± 0.001, -23.1 ± 2.1 mV, and 98.32 ± 2.37%, respectively. An in vitro release study and CCK-8 assays showed that CUR-DTX-L has better sustained release effects and antitumor efficacy than free drugs, the antitumor efficacy was verified by MCF-7 tumor-bearing mice, the CUR-DTX-L showed better antitumor efficacy than other groups, and the in vivo pharmacokinetic study indicated that the plasma concentration-time curve, mean residence time, and biological half-life time of CUR-DTX-L were significantly increased compared with free drugs, suggesting that it is a promising drug delivery system for the synergistic treatment of breast cancer.
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Affiliation(s)
- Xi Ye
- Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei, China
- Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
- Hefei Hospital Affiliated to Bengbu Medical College, Hefei, China
| | - Xin Chen
- Department of Pharmacy, Anhui Provincial Crops Hospital, Hefei, China
| | - Ruixi He
- Anhui University of Chinese Medicine, Hefei, China
- Institute of Drug Metabolism, School of Pharmaceutical Sciences, Anhui University of Chinese Medicine, Hefei, China
| | - Wangyang Meng
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weidong Chen
- Institute of Drug Metabolism, School of Pharmaceutical Sciences, Anhui University of Chinese Medicine, Hefei, China
| | - Fengling Wang
- Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei, China
- Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
- Hefei Hospital Affiliated to Bengbu Medical College, Hefei, China
| | - Xiangyun Meng
- Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei, China
- Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
- Hefei Hospital Affiliated to Bengbu Medical College, Hefei, China
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15
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Li C, Ma YQ. Prognostic significance of sex determining region Y-box 2, E-cadherin, and vimentin in esophageal squamous cell carcinoma. World J Clin Cases 2022; 10:9657-9669. [PMID: 36186174 PMCID: PMC9516931 DOI: 10.12998/wjcc.v10.i27.9657] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 06/30/2022] [Accepted: 08/21/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Sex determining region Y-box 2 (SOX2) can promote squamous cell carcinoma (SSC) because it regulates the migration and invasion of several different types of squamous carcinoma cells. However, few studies have examined the prognostic value of SOX2 and its effect on the epithelial-mesenchymal transition (EMT) in esophageal SSC (ESCC), a cancer characterized by high invasion and rapid metastasis.
AIM To verify the relationship of SOX2 and the EMT in ESCC and determine the prognostic value and significance of SOX2 and protein markers of the EMT in ESCC.
METHODS One hundred and eighty-five postsurgical ESCC patients were retrospectively examined. Immunohistochemistry was used to detect SOX2, E-cadherin, and vimentin in ESCC tissues. The chi-square test was used to determine the relationships of the expression of these proteins with clinical data. Kaplan-Meier survival curves were used to evaluate factors associated with overall survival (OS).
RESULTS SOX2 and vimentin had high expression in ESCC tissues and correlated with the depth of local carcinoma invasion. SOX2 expression had positive correlations with tumor size, vimentin expression, and the EMT, and a negative correlation with E-cadherin expression. Expression of SOX2 and vimentin had negative correlations with OS. SOX2 expression was an independent prognostic risk factor for poor OS in patients with ESCC.
CONCLUSION SOX2 expression was an independent risk factor for OS in patients with ESCC and its expression had a positive correlation with the expression of vimentin, a classic marker of the EMT. SOX2 promoted the migration and invasion of ESCC, and this may related to its effect on vimentin in promoting the EMT.
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Affiliation(s)
- Chao Li
- Department of RICU, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
| | - Yu-Qing Ma
- Department of Pathology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
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16
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Renal cell carcinoma management: A step to nano-chemoprevention. Life Sci 2022; 308:120922. [PMID: 36058262 DOI: 10.1016/j.lfs.2022.120922] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/12/2022] [Accepted: 08/26/2022] [Indexed: 11/21/2022]
Abstract
Renal cell carcinoma (RCC) is one of the most common kidney cancers, responsible for nearly 90 % of all renal malignancies. Despite the availability of many treatment strategies, RCC still remains to be an incurable disease due to its resistivity towards conventional therapies. Nanotechnology is an emerging field of science that offers newer possibilities in therapeutics including cancer medicine, specifically by targeted delivery of anticancer drugs. Several phytochemicals are known for their anti-cancer properties and have been regarded as chemopreventive agents. However, the hydrophobic nature of many phytochemicals decreases its bioavailability and distribution, thus showing limited therapeutic effect. Application of nanotechnology to enhance chemoprevention is an effective strategy to increase the bioavailability of phytochemicals and thereby its therapeutic efficacy. The present review focuses on the utility of nanotechnology in RCC treatment and chemopreventive agents of RCC. We have also visualized the future prospects of nanomolecules in the prevention and cure of RCC.
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17
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Ohishi T, Hayakawa S, Miyoshi N. Involvement of microRNA modifications in anticancer effects of major polyphenols from green tea, coffee, wine, and curry. Crit Rev Food Sci Nutr 2022; 63:7148-7179. [PMID: 35289676 DOI: 10.1080/10408398.2022.2038540] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Epidemiological studies have shown that consumption of green tea, coffee, wine, and curry may contribute to a reduced risk of various cancers. However, there are some cancer site-specific differences in their effects; for example, the consumption of tea or wine may reduce bladder cancer risk, whereas coffee consumption may increase the risk. Animal and cell-based experiments have been used to elucidate the anticancer mechanisms of these compounds, with reactive oxygen species (ROS)-based mechanisms emerging as likely candidates. Chlorogenic acid (CGA), curcumin (CUR), epigallocatechin gallate (EGCG), and resveratrol (RSV) can act as antioxidants that activate AMP-activated protein kinase (AMPK) to downregulate ROS, and as prooxidants to generate ROS, leading to the downregulation of NF-κB. Polyphenols can modulate miRNA (miR) expression, with these dietary polyphenols shown to downregulate tumor-promoting miR-21. CUR, EGCG, and RSV can upregulate tumor-suppressing miR-16, 34a, 145, and 200c, but downregulate tumor-promoting miR-25a. CGA, EGCG, and RSV downregulate tumor-suppressing miR-20a, 93, and 106b. The effects of miRs may combine with ROS-mediated pathways, enhancing the anticancer effects of these polyphenols. More precise analysis is needed to determine how the different modulations of miRs by polyphenols relate to the cancer site-specific differences found in epidemiological studies related to the consumption of foods containing these polyphenols.
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Affiliation(s)
- Tomokazu Ohishi
- Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Shizuoka, Japan
| | - Sumio Hayakawa
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Noriyuki Miyoshi
- Laboratory of Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan
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18
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Li S, Zhang W, Lan X, Tan L, Chen X, Lv KP, Huang Z, Gou L, Wan J, Meng X. High Biocompatible Poly(lactic-co-glycolic acid)-Based Nanosensitizer With Magnetic Resonance Imaging Capacity for Tumor Targeted Microwave Hyperthermia and Chemotherapy. J Biomed Nanotechnol 2022; 18:369-380. [PMID: 35484737 DOI: 10.1166/jbn.2022.3259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Microwave (MW) hyperthermia has been widely studied in tumor therapy, while the lack of specificity, and the potential toxicity induced by instability or difficulty in degradation of existed MW thermal sensitizers still limits the application. Herein, a new biocompatible Poly(lactic-co-glycolic acid) (PLGA)-based nanosensitizer of Dtxl-Gd@PLGA-PEG-TPP (DGPPT) with capacities of magnetic resonance (MR) imaging and mitochondrial targeting for MW hyperthermia combined with chemotherapy was constructed via a double emulsion solvent evaporation method. The modified TPP significantly enhanced the specificity of sensitizer for targeting mitochondria, a heat-sensitive energy supply plant in cells. Thus the MW thermal damage induced by the loaded Gd in PLGA nanospheres was also strengthened. Together, the system could also achieve MR imaging due to the existence of Gd. In addition, the encapsulated Dtxl performed the chemotherapy of inhibiting mitochondrial function for assisting with MW hyperthermia. In vivo experiments demonstrated that PLGA had high biocompatibility that no obvious damage occurred even the dose was up to 200 mg/kg. Meanwhile, DGPPT+MW representing the combination of mitochondrial targeting and MW hyperthermia-chemotherapy has also been proved to shrink tumor size effectively. This study provides a new direction for building biosafe and multifunctional MW sensitizer with active targeting ability to impede tumor growth.
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Affiliation(s)
- Shimei Li
- Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 29 Zhongguancun East Road, Beijing, 100190, P. R. China
| | - Wei Zhang
- Department of Interventional Radiology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, P. R. China
| | - Xudong Lan
- Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 29 Zhongguancun East Road, Beijing, 100190, P. R. China
| | - Longfei Tan
- Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 29 Zhongguancun East Road, Beijing, 100190, P. R. China
| | - Xudong Chen
- Department of Interventional Radiology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, P. R. China
| | - Kong-Peng Lv
- Department of Interventional Radiology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, P. R. China
| | - Zhongbing Huang
- College of Biomedical Engineering, Sichuan University, Chengdu, 610065, P. R. China
| | - Li Gou
- College of Biomedical Engineering, Sichuan University, Chengdu, 610065, P. R. China
| | - Jing Wan
- College of Chemistry & Environment, Southwest Minzu University, Chengdu, 610041, P. R. China
| | - Xianwei Meng
- Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 29 Zhongguancun East Road, Beijing, 100190, P. R. China
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19
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Di Chio C, Zhou M, Efferth T, Schirmeister T, Zappalà M, Ettari R. Synthesis and Cytotoxicity of Diarylpentanoids against Sensitive CCRF-CEM and Multidrug-Resistant CEM/ADR5000 Leukemia Cells. Chem Biodivers 2021; 19:e202100451. [PMID: 34871465 DOI: 10.1002/cbdv.202100451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 12/06/2021] [Indexed: 11/07/2022]
Abstract
This article described the synthesis and biological investigation of a series of symmetric diarylpentanoids, characterized by a dienone moiety and by a different pattern of substitution on the two phenyl rings. The series of compounds 1a-p were tested against drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 cells to evaluate their cytotoxic profile, and all the diarypentanoids revealed to be active against both the leukemia cell lines, with the best activity shown by compound 1o that showed a submicromolar activity against both CCRF-CEM and CEM/ADR5000 cell lines (EC50 =0.54 and 0.25 μM, respectively).
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Affiliation(s)
- Carla Di Chio
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Polo Annunziata, Viale SS. Annunziata, 98168, Messina, Italy
| | - Min Zhou
- Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany
| | - Thomas Efferth
- Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany
| | - Tanja Schirmeister
- Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany
| | - Maria Zappalà
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Polo Annunziata, Viale SS. Annunziata, 98168, Messina, Italy
| | - Roberta Ettari
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Polo Annunziata, Viale SS. Annunziata, 98168, Messina, Italy
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20
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Yan J, Shi L, Lin S, Li Y. MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel. Bioengineered 2021; 12:5334-5347. [PMID: 34415232 PMCID: PMC8806716 DOI: 10.1080/21655979.2021.1938497] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 05/31/2021] [Indexed: 12/24/2022] Open
Abstract
Development of chemoresistance remains a major challenge in treating patients suffering from esophageal squamous cell carcinoma (ESCC), despite treatment advances. MicroRNAs (miRNAs) have been shown to play critical roles in the regulation of ESCC cell chemoresistance. Here, we aimed to investigate the role of miR-624 in ESCC and its molecular mechanism in mediating the resistance of ESCC cells to two common chemotherapeutic drugs, cisplatin (CIS) and paclitaxel (PT). Expression patterns of miR-624, arrestin domain-containing 3 (ARRDC3), Yes-associated protein (YAP), and hypoxia-inducible factor-1α (HIF1α) in ESCC tissues and cell lines were identified using RT-qPCR and Western blot analysis. The binding affinities with the miR-624/ARRDC3/YAP/HIF1α axis were characterized. The chemotherapy-sensitive cell line KYSE150 and chemotherapy-resistant cell line KYSE410 were transfected with an overexpression plasmid or shRNA to study the effect of miR-624/ARRDC3/YAP/HIF1α axis on ESCC cell resistance to CIS and PT. Their in vivo effects on resistance to PT were assessed in tumor-bearing nude mice. High expression of miR-624, YAP and HIF1α, and low expression of ARRDC3 were observed in ESCC tissues and cell lines. miR-624 presented with higher expression in KYSE410 than in KYSE150 cells. miR-624 downregulated ARRDC3 to increase YAP and HIF1α expression so as to enhance ESCC cell resistance to CIS and PT in vitro and in vivo. Taken together, these data indicate an important role for miR-624 in promoting the chemoresistance of ESCC cells, highlighting a potential strategy to overcome drug resistance in ESCC treatment. miR-624 targets ARRDC3 to inhibit its expression, and consequently upregulates YAP expression by inhibiting degradation of YAP. By this mechanism, HIF1α expression is upregulated and the HIF1α signaling pathway is activated. ESCC cell chemotherapy resistance is eventually increased.
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Affiliation(s)
- Jie Yan
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China
| | - Litong Shi
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China
| | - Shan Lin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China
| | - Yi Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China
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21
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Shafabakhsh R, Arianfar F, Vosough M, Mirzaei HR, Mahjoubin-Tehran M, Khanbabaei H, Kowsari H, Shojaie L, Azar MEF, Hamblin MR, Mirzaei H. Autophagy and gastrointestinal cancers: the behind the scenes role of long non-coding RNAs in initiation, progression, and treatment resistance. Cancer Gene Ther 2021; 28:1229-1255. [PMID: 33432087 DOI: 10.1038/s41417-020-00272-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 10/06/2020] [Accepted: 11/23/2020] [Indexed: 02/07/2023]
Abstract
Gastrointestinal (GI) cancers comprise a heterogeneous group of complex disorders that affect different organs, including esophagus, stomach, gallbladder, liver, biliary tract, pancreas, small intestine, colon, rectum, and anus. Recently, an explosion in nucleic acid-based technologies has led to the discovery of long non-coding RNAs (lncRNAs) that have been found to possess unique regulatory functions. This class of RNAs is >200 nucleotides in length, and is characterized by their lack of protein coding. LncRNAs exert regulatory effects in GI cancer development by affecting different functions such as the proliferation and metastasis of cancer cells, apoptosis, glycolysis and angiogenesis. Over the past few decades, considerable evidence has revealed the important role of autophagy in both GI cancer progression and suppression. In addition, recent studies have confirmed a significant correlation between lncRNAs and the regulation of autophagy. In this review, we summarize how lncRNAs play a behind the scenes role in the pathogenesis of GI cancers through regulation of autophagy.
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Affiliation(s)
- Rana Shafabakhsh
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Farzaneh Arianfar
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Massoud Vosough
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 1665659911, Iran
| | - Hamid Reza Mirzaei
- Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Mahjoubin-Tehran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hashem Khanbabaei
- Medical Physics Department, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hamed Kowsari
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Layla Shojaie
- Research Center for Liver Diseases, Keck School of Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, USA
| | | | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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22
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Tagde P, Tagde P, Islam F, Tagde S, Shah M, Hussain ZD, Rahman MH, Najda A, Alanazi IS, Germoush MO, Mohamed HRH, Algandaby MM, Nasrullah MZ, Kot N, Abdel-Daim MM. The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders. Molecules 2021; 26:7109. [PMID: 34885693 PMCID: PMC8659038 DOI: 10.3390/molecules26237109] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/08/2021] [Accepted: 11/15/2021] [Indexed: 12/25/2022] Open
Abstract
Curcumin is the primary polyphenol in turmeric's curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin's bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.
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Affiliation(s)
- Priti Tagde
- Amity Institute of Pharmacy, Amity University, Noida 201303, India
- PRISAL Foundation (Pharmaceutical Royal International Society), Bhopa l462026, India;
| | - Pooja Tagde
- Practice of Medicine Department, Government Homeopathy College, Bhopa l462016, India;
| | - Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh;
| | - Sandeep Tagde
- PRISAL Foundation (Pharmaceutical Royal International Society), Bhopa l462026, India;
| | - Muddaser Shah
- Department of Botany, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
| | | | - Md. Habibur Rahman
- Department of Pharmacy, Southeast University, Banani, Dhaka 1213, Bangladesh
- Department of Global Medical Science, Graduate School, Yonsei University, Wonju 26426, Korea
| | - Agnieszka Najda
- Department of Vegetable and Herbal Crops, University of Life Sciences in Lublin, 50A Doświadczalna Street, 20-280 Lublin, Poland;
| | - Ibtesam S. Alanazi
- Department of Biology, Faculty of Sciences, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia;
| | - Mousa O. Germoush
- Biology Department, College of Science, Jouf University, Sakaka P.O. Box 2014, Saudi Arabia;
| | - Hanan R. H. Mohamed
- Zoology Department, Faculty of Science, Cairo University, Giza 12613, Egypt;
| | - Mardi M. Algandaby
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Mohammed Z. Nasrullah
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Natalia Kot
- Department of Landscape Architecture, University of Life Science in Lublin, 28 Gleboka Street, 20-612 Lublin, Poland;
| | - Mohamed M. Abdel-Daim
- Pharmacy Program, Department of Pharmaceutical Sciences, Batterjee Medical College, Jeddah 21442, Saudi Arabia
- Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
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Bagherian A, Roudi B, Masoudian N, Mirzaei H. Anti-glioblastoma effects of nanomicelle-curcumin plus erlotinib. Food Funct 2021; 12:10926-10937. [PMID: 34647945 DOI: 10.1039/d1fo01611c] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Glioblastoma (GBM), one of the most significant brain neoplasms, is characterized by high metastasis and recurrence. Crossing the blood-brain barrier is one of the main therapeutic obstacles, seriously hampering therapeutic agents entering the brain. This research investigated the co-delivery of erlotinib and curcumin via nanomicelles for enhancing anti-GBM treatment in vitro. For this purpose, curcumin and nanomicelle-curcumin (50 μM) were investigated alone and also with erlotinib (50 μM) in U87 glioblastoma cells. The cell viability of U87 cells after exposure to curcumin/nanomicelle curcumin/erlotinib and their combinations was measured by CCK-8 assay. The expression of the Wnt signaling-related genes was measured by qRT-PCR assay. The altered expression of NF-kB and proteins associated with angiogenesis, apoptosis, and autophagy were investigated by western blot assay. Compared with the control, all treatments reduced the viability of U87 glioblastoma cells. Furthermore, the level of proteins related to angiogenesis and Wnt pathway-associated genes in the nanomicelle-curcumin + erlotinib group were significantly decreased compared to the curcumin, erlotinib, and control groups. Each treatment regulated autophagy and apoptosis-associated proteins. Total phospho-NF-κB (p65) and total NF-κB (p65) declined in each treatment at the protein levels. Overall, nanomicelle-curcumin alone or combined with erlotinib showed anti-GBM activity in the U87 cell line by regulating the signaling pathways in GBM pathogenesis and thus may be a promising nanodrug candidate for application in the field of GBM therapy.
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Affiliation(s)
- Ali Bagherian
- Department of Biology, Faculty of Science, Islamic Azad University, Damghan Branch, Damghan, Iran.
| | - Bostan Roudi
- Department of Biology, Faculty of Science, Islamic Azad University, Damghan Branch, Damghan, Iran.
| | - Nahid Masoudian
- Department of Biology, Faculty of Science, Islamic Azad University, Damghan Branch, Damghan, Iran.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran.
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24
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Guo Y, Liang J, Liu B, Jin Y. Molecular Mechanism of Food-Derived Polyphenols on PD-L1 Dimerization: A Molecular Dynamics Simulation Study. Int J Mol Sci 2021; 22:ijms222010924. [PMID: 34681584 PMCID: PMC8535905 DOI: 10.3390/ijms222010924] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 09/30/2021] [Accepted: 10/02/2021] [Indexed: 01/18/2023] Open
Abstract
In cancer immunotherapy, an emerging approach is to block the interactions of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) using small-molecule inhibitors. The food-derived polyphenols curcumin (CC), resveratrol (RSV) and epigallocatechin gallate (EGCG) have anticancer immunologic functions, which, recently, have been proposed to act via the downregulation of PD-L1 expression. However, it remains unclear whether they can directly target PD-L1 dimerization and, thus, interrupt the PD-1/PD-L1 pathway. To elucidate the molecular mechanism of such compounds on PD-L1 dimerization, molecular docking and nanosecond molecular dynamics simulations were performed. Binding free energy calculations show that the affinities of CC, RSV and EGCG to the PD-L1 dimer follow a trend of CC > RSV > EGCG. Hence, CC is the most effective inhibitor of the PD-1/PD-L1 pathway. Analysis on contact numbers, nonbonded interactions and residue energy decomposition indicate that such compounds mainly interact with the C-, F- and G-sheet fragments of the PD-L1 dimer, which are involved in interactions with PD-1. More importantly, nonpolar interactions between these compounds and the key residues Ile54, Tyr56, Met115, Ala121 and Tyr123 play a dominant role in binding. Free energy landscape and secondary structure analyses further demonstrate that such compounds can stably interact with the binding domain of the PD-L1 dimer. The results provide evidence that CC, RSV and EGCG can inhibit PD-1/PD-L1 interactions by directly targeting PD-L1 dimerization. This provides a novel approach to discovering food-derived small-molecule inhibitors of the PD-1/PD-L1 pathway with potential applications in cancer immunotherapy.
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Deng L, Zhang X, Xiang X, Xiong R, Xiao D, Chen Z, Liu K, Feng G. NANOG Promotes Cell Proliferation, Invasion, and Stemness via IL-6/STAT3 Signaling in Esophageal Squamous Carcinoma. Technol Cancer Res Treat 2021; 20:15330338211038492. [PMID: 34520294 PMCID: PMC8723181 DOI: 10.1177/15330338211038492] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background: Cancer cells have properties similar to those of stem cells, including high proliferation and self-renewal ability. NANOG is the key regulatory gene that maintains the self-renewal and pluripotency characteristics of embryonic stem cells. We previously reported that knockdown of the pluripotent stem cell factor NANOG obviously reduced the proliferation and drug-resistance capabilities of esophageal squamous cell carcinoma (ESCC). In this study, we gained insights into the potential regulatory mechanism of NANOG, particularly in ESCC. Methods: NANOG was ectopically expressed in the Eca-109 cell line via pcDNA3.1 vector transfection. The mRNA expression of different genes was detected using quantitative real-time polymerase chain reaction, and protein quantification was performed by western blotting. The enzyme-linked immunosorbent assay was used to detect the expression of interleukin 6 (IL-6). The capabilities of proliferation, migration, and invasion were investigated using cell count and Transwell assays. The tumor sphere-forming assay was used to investigate the sphere formation capacity of cancer stem cells. Results: The expression of NANOG promoted the cell proliferation and sphere formation capacity of cancer stem cells in a dose-dependent manner. IL-6-mediated activation of signal transducer and activator of transcription 3 (STAT3) was closely related to the expression of NANOG in ESCC. Consistently, the target genes of STAT3, including CCL5, VEGFA, CCND1, and Bcl-xL, were upregulated upon the overexpression of NANOG. Conclusion: These results revealed that the expression of NANOG promotes cell proliferation, invasion, and stemness via IL-6/STAT3 signaling in ESCC.
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Affiliation(s)
- Li Deng
- Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, 74655The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China.,School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of China
| | - Xinping Zhang
- Department of Oncology, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xiaocong Xiang
- Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, 74655The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
| | - Rong Xiong
- Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, 74655The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
| | - Dongqin Xiao
- Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, 74655The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
| | - Zhu Chen
- Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, 74655The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
| | - Kang Liu
- Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, 74655The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
| | - Gang Feng
- Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, 74655The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
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Wang J, Luo FF, Huang TJ, Mei Y, Peng LX, Qian CN, Huang BJ. The upregulated expression of RFC4 and GMPS mediated by DNA copy number alteration is associated with the early diagnosis and immune escape of ESCC based on a bioinformatic analysis. Aging (Albany NY) 2021; 13:21758-21777. [PMID: 34520390 PMCID: PMC8457608 DOI: 10.18632/aging.203520] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 08/31/2021] [Indexed: 12/24/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is a malignant tumor that commonly occurs worldwide. Usually, Asia, especially China, has a high incidence of esophageal cancer. ESCC often has a poor outcome because of a late diagnosis and lack of effective treatments. To build foundations for the early diagnosis and treatment of ESCC, we used the gene expression datasets GSE20347 and GSE17351 from the GEO database and a private dataset to uncover differentially expressed genes (DEGs) and key genes in ESCC. Notably, we found that replication factor C subunit 4 (RFC4) and guanine monophosphate synthase (GMPS) were upregulated but have been rarely studied in ESCC. In particular, to the best of our knowledge, our study is the first to explore GMPS and ESCC. Furthermore, we found that high levels of RFC4 and GMPS expression may result from an increase in DNA copy number alterations. Furthermore, RFC4 and GMPS were both upregulated in the early stage and early nodal metastases of esophageal carcinoma. The expression of RFC4 was strongly correlated with GMPS. In addition, we explored the relationship between RFC4 and GMPS expression and tumor-infiltrating immune cells (TILs) in esophageal carcinoma. The results showed that the levels of RFC4 and GMPS increased with a decrease in some tumor-infiltrating cells. Upregulated RFC4 and GMPS with high TILs indicate a worse prognosis. In summary, our study shows that RFC4 and GMPS have potential as biomarkers for the early diagnosis of ESCC and may played a crucial role in the process of tumor immunity in ESCC.
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Affiliation(s)
- Jing Wang
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China
| | - Fei-Fei Luo
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China
| | - Tie-Jun Huang
- Department of Nuclear Medicine, The Second People's Hospital of Shenzhen, Shenzhen 518037, People's Republic of China
| | - Yan Mei
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China
| | - Li-Xia Peng
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China
| | - Chao-Nan Qian
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China.,Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China
| | - Bi-Jun Huang
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China
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Tan L, Cheng D, Wen J, Huang K, Zhang Q. Identification of prognostic hypoxia-related genes signature on the tumor microenvironment in esophageal cancer. MATHEMATICAL BIOSCIENCES AND ENGINEERING : MBE 2021; 18:7743-7758. [PMID: 34814273 DOI: 10.3934/mbe.2021384] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
BACKGROUND Hypoxia is a crucial factor in the development of esophageal cancer. The relationship between hypoxia and immune status in the esophageal cancer microenvironment is becoming increasingly important in clinical practice. This study aims to clarify and investigate the possible connection between immunotherapy and hypoxia in esophageal cancer. METHODS The Cancer Genome Atlas databases are used to find two types of esophageal cancer cases. Cox regressions analyses are used to screen genes for hypoxia-related traits. After that, the genetic signature is validated by survival analysis and the construction of ROC curves. GSEA is used to compare differences in enrichment in the two groups and is followed by the CIBERSORT tool to investigate a potentially relevant correlation between immune cells and gene signatures. RESULTS We found that the esophageal adenocarcinoma hypoxia model contains 3 genes (PGK1, PGM1, SLC2A3), and the esophageal squamous cell carcinoma hypoxia model contains 2 genes (EGFR, ATF3). The findings demonstrated that the survival rate of patients in the high-risk group is lower than in the lower-risk group. Furthermore, we find that three kinds of immune cells (memory activated CD4+ T cells, activated mast cells, and M2 macrophages) have a marked infiltration in the tissues of patients in the high-risk group. Moreover, we find that PD-L1 and CD244 are highly expressed in high-risk groups. CONCLUSIONS Our data demonstrate that oxygen deprivation is correlated with prognosis and the incidence of immune cell infiltration in patients with both types of esophageal cancer, which provides an immunological perspective for the development of personalized therapy.
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Affiliation(s)
- Linlin Tan
- The Affiliated People's Hospital of Ningbo University, Cardiothoracic Surgery Department, Ningbo, Zhejiang, China
| | - Dingzhuo Cheng
- Ningbo NO6. Hospital, Neurosurgery Department, Ningbo, Zhejiang, China
| | - Jianbo Wen
- The Affiliated People's Hospital of Ningbo University, Cardiothoracic Surgery Department, Ningbo, Zhejiang, China
| | - Kefeng Huang
- The Affiliated People's Hospital of Ningbo University, Cardiothoracic Surgery Department, Ningbo, Zhejiang, China
| | - Qin Zhang
- The Affiliated People's Hospital of Ningbo University, Cardiothoracic Surgery Department, Ningbo, Zhejiang, China
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Chen ZX, Li GS, Yang LH, Liu HC, Qin GM, Shen L, He WY, Gan TQ, Li JJ. Upregulation of BIRC5 plays essential role in esophageal squamous cell carcinoma. MATHEMATICAL BIOSCIENCES AND ENGINEERING : MBE 2021; 18:6941-6960. [PMID: 34517565 DOI: 10.3934/mbe.2021345] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, the detection and prognosis of which are still unsatisfactory. Thus, it is essential to explore the factors that may identify ESCC and evaluate the prognosis of ESCC patients. RESULTS Both protein and mRNA expression levels of BIRC5 are upregulated in ESCC group rather than non-ESCC group (standardized mean difference > 0). BIRC5 mRNA expression is related to the age, tumor location, lymph node stage and clinical stage of ESCC patients (p < 0.05). BIRC5 expression makes it feasible to distinguish ESCC from non-ESCC (area under the curve > 0.9), and its high expression is related to poor prognosis of ESCC patients (restrictive survival time difference = -0.036, p < 0.05). BIRC5 may play an important role in ESCC by influencing the cell cycle pathway, and CDK1, MAD2L and CDC20 may be the hub genes of this pathway. The transcription factors-MAZ and TFPD1 -are likely to regulate the transcription of BIRC5, which may be one of the factors for the high expression of BIRC5 in ESCC. CONCLUSIONS The current study shows that upregulation of BIRC5 may have essential clinical value in ESCC, and contributes to the understanding of the pathogenesis of ESCC.
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Affiliation(s)
- Zu-Xuan Chen
- Department of Medical Oncology, Second Affiliated Hospital of Guangxi Medical University, 166 DaxueXi Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, P. R. China
| | - Guo-Sheng Li
- Department of Medical Oncology, Second Affiliated Hospital of Guangxi Medical University, 166 DaxueXi Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, P. R. China
| | - Li-Hua Yang
- Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, P. R. China
| | - He-Chuan Liu
- Department of Medical Oncology, Second Affiliated Hospital of Guangxi Medical University, 166 DaxueXi Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, P. R. China
| | - Guang-Mei Qin
- Department of Medical Oncology, Second Affiliated Hospital of Guangxi Medical University, 166 DaxueXi Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, P. R. China
| | - Lang Shen
- Department of Medical Oncology, Second Affiliated Hospital of Guangxi Medical University, 166 DaxueXi Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, P. R. China
| | - Wei-Ying He
- Department of Medical Oncology, Second Affiliated Hospital of Guangxi Medical University, 166 DaxueXi Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, P. R. China
| | - Ting-Qing Gan
- Department of Medical Oncology, Second Affiliated Hospital of Guangxi Medical University, 166 DaxueXi Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, P. R. China
| | - Jian-Jun Li
- Department of General Surgery, Second Affiliated Hospital of Guangxi Medical University, 166 DaxueXi Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, P. R. China
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Recent advances of m 6A methylation modification in esophageal squamous cell carcinoma. Cancer Cell Int 2021; 21:421. [PMID: 34376206 PMCID: PMC8353866 DOI: 10.1186/s12935-021-02132-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 08/03/2021] [Indexed: 12/17/2022] Open
Abstract
In recent years, with the development of RNA sequencing technology and bioinformatics methods, the epigenetic modification of RNA based on N6-methyladenosine (m6A) has gradually become a research hotspot in the field of bioscience. m6A is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs). m6A methylation modification can dynamically and reversibly regulate RNA transport, localization, translation and degradation through the interaction of methyltransferase, demethylase and reading protein. m6A methylation can regulate the expression of proto-oncogenes and tumor suppressor genes at the epigenetic modification level to affect tumor occurrence and metastasis. The morbidity and mortality of esophageal cancer (EC) are still high worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common tissue subtype of EC. This article reviews the related concepts, biological functions and recent advances of m6A methylation in ESCC, and looks forward to the prospect of m6A methylation as a new diagnostic biomarker and potential therapeutic target for ESCC.
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30
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Sun Q, He M, Zhang M, Zeng S, Chen L, Zhao H, Yang H, Liu M, Ren S, Xu H. Traditional Chinese Medicine and Colorectal Cancer: Implications for Drug Discovery. Front Pharmacol 2021; 12:685002. [PMID: 34276374 PMCID: PMC8281679 DOI: 10.3389/fphar.2021.685002] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 06/09/2021] [Indexed: 12/24/2022] Open
Abstract
As an important part of complementary and alternative medicine, traditional Chinese medicine (TCM) has been applied to treat a host of diseases for centuries. Over the years, with the incidence rate of human colorectal cancer (CRC) increasing continuously and the advantage of TCM gradually becoming more prominent, the importance of TCM in both domestic and international fields is also growing with each passing day. However, the unknowability of active ingredients, effective substances, and the underlying mechanisms of TCM against this malignant tumor greatly restricts the translation degree of clinical products and the pace of precision medicine. In this review, based on the characteristics of TCM and the oral administration of most ingredients, we herein provide beneficial information for the clinical utilization of TCM in the prevention and treatment of CRC and retrospect the current preclinical studies on the related active ingredients, as well as put forward the research mode for the discovery of active ingredients and effective substances in TCM, to provide novel insights into the research and development of innovative agents from this conventional medicine for CRC treatment and assist the realization of precision medicine.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Haibo Xu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Akbari A, Sedaghat M, Heshmati J, Tabaeian SP, Dehghani S, Pizarro AB, Rostami Z, Agah S. Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers. Biomed Pharmacother 2021; 141:111849. [PMID: 34214729 DOI: 10.1016/j.biopha.2021.111849] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 06/08/2021] [Accepted: 06/24/2021] [Indexed: 02/07/2023] Open
Abstract
Curcumin is a bioactive ingredient found in the Rhizomes of Curcuma longa. Curcumin is well known for its chemopreventive and anti-cancer properties. Recent findings have demonstrated several pharmacological and biological impacts of curcumin, related to the control and the management of gastrointestinal cancers. Mechanistically, curcumin exerts its biological impacts via antioxidant and anti-inflammatory effects through the interaction with various transcription factors and signaling molecules. Moreover, epigenetic modulators such as microRNAs (miRNAs) have been revealed as novel targets of curcumin. Curcumin was discovered to regulate the expression of numerous pathogenic miRNAs in gastric, colorectal, esophageal and liver cancers. The present systematic review was performed to identify miRNAs that are modulated by curcumin in gastrointestinal cancers.
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Affiliation(s)
- Abolfazl Akbari
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Meghdad Sedaghat
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Javad Heshmati
- Songhor Healthcare Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Seidamir Pasha Tabaeian
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Sadegh Dehghani
- Radiation Sciences Department, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Zahra Rostami
- Department of Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.
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32
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Taghvaei F, Rastin SJ, Milani AT, Khameneh ZR, Hamini F, Rasouli MA, Asghari K, Rekabi Shishavan AM, Ebrahimifar M, Rashidi S. Carboplatin and epigallocatechin-3-gallate synergistically induce cytotoxic effects in esophageal cancer cells. Res Pharm Sci 2021; 16:240-249. [PMID: 34221057 PMCID: PMC8216160 DOI: 10.4103/1735-5362.314822] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 10/20/2020] [Accepted: 03/17/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND AND PURPOSE We aimed at evaluating the effects of combinatorial treatments with carboplatin and epigallocatechin-3-gallate (EGCG) on the KYSE-30 esophageal cancer (EC) cell line and elucidate the underlying mechanisms. EXPERIMENTAL APPROACH EC cells were harvested and exposed to increasing concentrations of carboplatin and EGCG to construct a dose-response plot. Cell inhibitory effects were assessed by the MTT method and apoptosis-related gene expression levels (caspases 8 and 9) and Bcl-2 mRNA were detected using real-time polymerase chain reaction. The lactate levels in the various treated cases were analyzed using the colorimetric assay kit. In addition, total antioxidant capacity was measured. FINDINGS/RESULTS The results indicated that, following treatments with carboplatin in IC20, IC25, and IC10 concentrations when combined with EGCG in similar concentrations, synergistically decreased cell viability versus single treatments of both agents. Also, in combined treatments at IC20 and IC25 of both agents the gene expression ratio of caspases 8 and 9 upregulated significantly compared to monotherapies (P < 0.05). Bcl-2 gene expression ratios were decreased in double agents treated cells versus monotherapies. Following treatment of KYSE-30 cells with carboplatin and EGCG in double combinations, lactate levels were significantly decreased compared with the untreated cells and single treatments (P < 0.05). Also, in IC25, IC20, and IC10 concentrations of both agents the total antioxidant capacity levels were decreased versus monotherapies and untreated cells. CONCLUSION AND IMPLICATIONS The presented study determined that treatment with carboplatin and EGCG was capable of promoting cytotoxicity in EC cells and inhibits the cancer progress. Combined treatments with low concentrations of carboplatin and EGCG may promote apoptosis induction and inhibit cell growth. These results confirmed the anticancer effects of carboplatin and EGCG and providing a base for additional use of EGCG to the EC treatment.
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Affiliation(s)
- Fatemeh Taghvaei
- Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Science, Yazd, I.R. Iran
| | - Sepideh Jafarzadeh Rastin
- Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Science, Yazd, I.R. Iran
| | - Attabak Toofani Milani
- Department of Biochemistry, Medicine Faculty, Tabriz Branch, Islamic Azad University, Tabriz, I.R. Iran
| | - Zakieh Rostamzadeh Khameneh
- Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, I.R. Iran
| | - Forough Hamini
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Urmia University of Medical Sciences, Urmia, I.R. Iran
| | - Mohammad Aziz Rasouli
- Vice Chancellor for Educational and Research, Kowsar Hospital, Kurdistan University of Medical Sciences, Sanandaj, I.R. Iran
| | - Keivan Asghari
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Urmia University of Medical Sciences, Urmia, I.R. Iran
| | - Amir Mohammad Rekabi Shishavan
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Urmia University of Medical Sciences, Urmia, I.R. Iran
| | - Meysam Ebrahimifar
- Department of Toxicology, Faculty of Pharmacy, Shahreza Azad University, Shahreza, I.R. Iran
| | - Siamak Rashidi
- Tohid Hospital, Kurdistan University of Medical Sciences, Sanandaj, I.R. Iran
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Nazarian H, Novin MG, Khaleghi S, Habibi B. Small non-coding RNAs in embryonic pre-implantation. Curr Mol Med 2021; 22:287-299. [PMID: 34042034 DOI: 10.2174/1566524021666210526162917] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 04/02/2021] [Accepted: 04/03/2021] [Indexed: 11/22/2022]
Abstract
Failure of embryo implantation has been introduced as an important limiting parameter in early assisted reproduction and pregnancy. The embryo-maternal interactions, endometrial receptivity, and detections of implantation consist of the embryo viability. For regulating the implantation, multiple molecules may be consisted, however, their specific regulatory mechanisms still stand unclear. MicroRNAs (miRNAs) have been highly concerned due to their important effect on human embryo implantation. MicroRNA (miRNA), which acts as the transcriptional regulator of gene expression, is consisted in embryo implantation. Scholars determined that miRNAs cannot affect the cells and release by cells in the extracellular environment considering facilitating intercellular communication, multiple packaging forms, and preparing indicative data in the case of pathological and physiological conditions. The detection of extracellular miRNAs provided new information in cases of implantation studies. For embryo-maternal communication, MiRNAs offered novel approaches. In addition, in assisted reproduction, for embryo choice and prediction of endometrial receptivity, they can act as non-invasive biomarkers and can enhance the accuracy in the process of reducing the mechanical damage for the tissue.
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Affiliation(s)
- Hamid Nazarian
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marefat Ghaffari Novin
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Khaleghi
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bahare Habibi
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Tavakoli F, Khatami SS, Momeni F, Azadbakht J, Ghasemi F. Cervical Cancer Diagnosis: Insights into Biochemical Biomarkers and Imaging Techniques. Comb Chem High Throughput Screen 2021; 24:605-623. [PMID: 32875976 DOI: 10.2174/1386207323666200901101955] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 07/14/2020] [Accepted: 08/06/2020] [Indexed: 11/22/2022]
Abstract
Cervical malignancy is known as one of the important cancers which is originated from cervix. This malignancy has been observed in women infected with papillomavirus who had regular oral contraceptives, multiple pregnancies, and sexual relations. Early and fast cervical cancer diagnosis is known as two important aspects of cervical cancer therapy. Several investigations indicated that early and fast detection of cervical cancer could be associated with better treatment process and increasing survival rate of patients with this malignancy. Imaging techniques are very important diagnosis tools that could be employed for diagnosis and following responses to therapy in various cervical cancer stages. Multiple lines of evidence indicated that utilization of imaging techniques is related to some limitations (i.e. high cost, and invasive effects). Hence, it seems that along with using imaging techniques, finding and developing new biomarkers could be useful in the diagnosis and treatment of subjects with cervical cancer. Taken together, many studies showed that a variety of biomarkers including, several proteins, mRNAs, microRNAs, exosomes and polymorphisms might be introduced as prognostic, diagnostic and therapeutic biomarkers in cervical cancer therapy. In this review article, we highlighted imaging techniques as well as novel biomarkers for the diagnosis of cervical cancer.
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Affiliation(s)
- Fatemeh Tavakoli
- Department of Biotechnology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Sadat Khatami
- Department of Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Fatemeh Momeni
- Isfahan Research Committee of Multiple Sclerosis, Alzahra Research Institute, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Javid Azadbakht
- Department of Radiology and Imaging, Kashan University of Medical Science, Kashan, Iran
| | - Faezeh Ghasemi
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
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Sethiya A, Agarwal DK, Agarwal S. Current Trends in Drug Delivery System of Curcumin and its Therapeutic Applications. Mini Rev Med Chem 2021; 20:1190-1232. [PMID: 32348221 DOI: 10.2174/1389557520666200429103647] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/30/2020] [Accepted: 04/09/2020] [Indexed: 02/07/2023]
Abstract
Curcumin is a poly phenolic compound extracted from turmeric. Over the past years, it has acquired significant interest among researchers due to its numerous pharmacological activities like anti- cancer, anti-alzheimer, anti-diabetic, anti-bacterial, anti-inflammatory and so on. However, the clinical use of curcumin is still obstructed due to tremendously poor bioavailability, rapid metabolism, lower gastrointestinal absorption, and low permeability through cell that makes its pharmacology thrilling. These issues have led to enormous surge of investigation to develop curcumin nano formulations which can overcome these restrictive causes. The scientists all across the universe are working on designing several drug delivery systems viz. liposomes, micelles, magnetic nano carriers, etc. for curcumin and its composites which not only improve its physiochemical properties but also enhanced its therapeutic applications. The review aims to systematically examine the treasure of information about the medicinal use of curcumin. This article delivers a general idea of the current study piloted to overwhelm the complications with the bioavailability of curcumin which have exhibited an enhanced biological activity than curcumin. This article explains the latest and detailed study of curcumin and its conjugates, its phytochemistry and biological perspectives and also proved curcumin as an efficient drug candidate for the treatment of numerous diseases. Recent advancements and futuristic viewpoints are also deliberated, which shall help researchers and foster commercial translations of improved nanosized curcumin combination for the treatment of various diseases.
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Affiliation(s)
- Ayushi Sethiya
- Department of Chemistry, Synthetic Organic Chemistry Laboratory, MLS University, Udaipur, 313001, India
| | | | - Shikha Agarwal
- Department of Chemistry, Synthetic Organic Chemistry Laboratory, MLS University, Udaipur, 313001, India
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LINC00657/miR-26a-5p/CKS2 ceRNA network promotes the growth of esophageal cancer cells via the MDM2/p53/Bcl2/Bax pathway. Biosci Rep 2021; 40:224733. [PMID: 32426838 PMCID: PMC7268253 DOI: 10.1042/bsr20200525] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/11/2020] [Accepted: 05/13/2020] [Indexed: 02/07/2023] Open
Abstract
LncRNA LINC00657 has oncogenic or anti-carcinoma roles in different cancers, and yet its detailed molecular mechanism in esophageal cancer (EC) remains unclear. In addition, competitive endogenous RNA (ceRNA) regulatory lncRNA–miRNA–mRNA networks are critical for tumorigenesis and progression. Hence, the present study explored the roles of LINC00657 in EC and identified its relevant ceRNA network. We first detected the expression of LINC00657 in EC. Then, we applied starBase and TargetScan websites to find miR-26a-5p binding to LINC00657 and obtain CKS2 as a target of miR-26a-5p. The roles of LINC00657, miR-26a-5p or CKS2 in the proliferation, migration, invasion, and apoptosis of EC cells were respectively assessed by CCK-8, wound healing assay, transwell invasion assay, and flow cytometry. The changes of the MDM2/p53/Bcl2/Bax pathway were measured via Western blot. The results revealed that LINC00657 showed an aberrant high expression in EC cells, which promoted the growth of EC cells. Additionally, LINC00657 functioned as a sponge of miR-26a-5p, and LINC00657 negatively mediated miR-26a-5p to regulate the growth of EC cells. Furthermore, CKS2 was observed as a direct target of miR-26a-5p, and CKS2 controlled the growth of EC cells via the MDM2/p53/Bcl2/Bax pathway. Moreover, there was a positive correlation between LINC00657 and CKS2. LINC00657 knockdown inhibited CKS2 expression to suppress the proliferation, migration, and invasion of EC cells and induced apoptosis via regulating the MDM2/p53/Bcl2/Bax pathway. Collectively, LINC00657/miR-26a-5p/CKS2 ceRNA network could promote the progression of EC, which is good for understanding the molecular mechanism of EC and offers novel biomarkers for EC diagnosis and therapy.
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Anticancer Mechanism of Curcumin on Human Glioblastoma. Nutrients 2021; 13:nu13030950. [PMID: 33809462 PMCID: PMC7998496 DOI: 10.3390/nu13030950] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 12/13/2022] Open
Abstract
Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin’s anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.
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CTCF-silenced miR-137 contributes to EMT and radioresistance in esophageal squamous cell carcinoma. Cancer Cell Int 2021; 21:155. [PMID: 33685449 PMCID: PMC7938596 DOI: 10.1186/s12935-020-01740-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 12/25/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in gastrointestinal system. MicroRNAs (miRNAs) have been reported to be implicated in cancer development. However, the role of miR-137 has not been fully revealed in ESCC. METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were separately used to examine RNA level and protein level. 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell assays and flow cytometry analyses were conducted to assess biological behaviors of ESCC cells. Additionally, the interaction between genes were analyzed via Chromatin Immunoprecipitation (ChIP) assay, RNA Binding Protein Immunoprecipitation (RIP) assay, RNA pull down assay and luciferase reporter assay. RESULTS MiR-137 was down-regulated in ESCC cells. Upregulation of miR-137 hindered ESCC cell proliferation, migration, invasion and epithelial mesenchymal transition (EMT). Besides, miR-137 enhanced the sensitivity of ESCC cells to irradiation. Moreover, CCCTC-binding factor (CTCF) inactivated miR-137 transcription in ESCC cells. Furthermore, we revealed enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and paxillin (PXN) as the downstream targets of miR-137. In turn, EZH2 was recruited by CTCF and induced methylation in miR-137 promoter. CONCLUSION CTCF/Suz12/EZH2 complex-silenced miR-137 facilitates ESCC progression and radioresistance by targeting EZH2 and PXN.
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Wu R, Zhuang H, Mei YK, Sun JY, Dong T, Zhao LL, Fan ZN, Liu L. Systematic identification of key functional modules and genes in esophageal cancer. Cancer Cell Int 2021; 21:134. [PMID: 33632229 PMCID: PMC7905886 DOI: 10.1186/s12935-021-01826-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 02/09/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Esophageal cancer is associated with high incidence and mortality worldwide. Differential expression genes (DEGs) and weighted gene co-expression network analysis (WGCNA) are important methods to screen the core genes as bioinformatics methods. METHODS The DEGs and WGCNA were combined to screen the hub genes, and pathway enrichment analyses were performed on the hub module in the WGCNA. The CCNB1 was identified as the hub gene based on the intersection between DEGs and the greenyellow module in WGCNA. Expression levels and prognostic values of CCNB1 were verified in UALCAN, GEPIA2, HCMDB, Kaplan-Meier plotter, and TIMER databases. RESULTS We identified 1,044 DEGs from dataset GSE20347, 1,904 from GSE29001, and 2,722 from GSE111044, and 32 modules were revealed by WGCNA. The greenyellow module was identified as the hub module in the WGCNA. CCNB1 gene was identified as the hub gene, which was upregulated in tumour tissues. Moreover, esophageal cancer patients with higher expression of CCNB1 showed a worse prognosis. However, CCNB1 'might not play an important role in immune cell infiltration. CONCLUSIONS Based on DEGs and key modules related to esophageal cancer, CCNB1 was identified as the hub gene, which offered novel insights into the development and treatment of esophageal cancer.
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Affiliation(s)
- Rui Wu
- Department of Digestive Endoscopy, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Hao Zhuang
- Department of Digestive Endoscopy, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Yu-Kun Mei
- Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, China
| | - Jin-Yu Sun
- Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Tao Dong
- Department of Digestive Endoscopy, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Li-Li Zhao
- Department of Digestive Endoscopy, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China
| | - Zhi-Ning Fan
- Department of Digestive Endoscopy, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
| | - Li Liu
- Department of Digestive Endoscopy, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
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Pourhanifeh MH, Mottaghi R, Razavi ZS, Shafiee A, Hajighadimi S, Mirzaei H. Therapeutic Applications of Curcumin and its Novel Formulations in the Treatment of Bladder Cancer: A Review of Current Evidence. Anticancer Agents Med Chem 2021; 21:587-596. [PMID: 32767956 DOI: 10.2174/1871520620666200807223832] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 02/26/2020] [Accepted: 05/04/2020] [Indexed: 11/22/2022]
Abstract
Bladder cancer, a life-threatening serious disease, is responsible for thousands of cancer-associated deaths worldwide. Similar to other malignancies, standard treatments of bladder cancer, such as Chemoradiotherapy, are not efficient enough in the affected patients. It means that, according to recent reports in the case of life quality as well as the survival time of bladder cancer patients, there is a critical requirement for exploring effective treatments. Recently, numerous investigations have been carried out to search for appropriate complementary treatments or adjuvants for bladder cancer therapy. Curcumin, a phenolic component with a wide spectrum of biological activities, has recently been introduced as a potential anti-cancer agent. It has been shown that this agent exerts its therapeutic effects via targeting a wide range of cellular and molecular pathways involved in bladder cancer. Herein, the current data on curcumin therapy for bladder cancer are summarized.
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Affiliation(s)
| | - Reza Mottaghi
- Department of Oral and Maxillofacial Surgery, Kashan University of Medical Sciences, Kashan, Iran
| | - Zahra S Razavi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Alimohammad Shafiee
- Division of General Internal Medicine, Toronto General Hospital, Toronto, ON, Canada
| | - Sarah Hajighadimi
- Division of General Internal Medicine, Toronto General Hospital, Toronto, ON, Canada
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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Mirzaei H, Bagheri H, Ghasemi F, Khoi JM, Pourhanifeh MH, Heyden YV, Mortezapour E, Nikdasti A, Jeandet P, Khan H, Sahebkar A. Anti-Cancer Activity of Curcumin on Multiple Myeloma. Anticancer Agents Med Chem 2021; 21:575-586. [PMID: 32951583 DOI: 10.2174/1871520620666200918113625] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 06/26/2020] [Accepted: 06/30/2020] [Indexed: 12/24/2022]
Abstract
Multiple Myeloma (MM) is the third most common and deadly hematological malignancy, which is characterized by a progressive monoclonal proliferation within the bone marrow. MM is cytogenetically heterogeneous with numerous genetic and epigenetic alterations, which lead to a wide spectrum of signaling pathways and cell cycle checkpoint aberrations. MM symptoms can be attributed to CRAB features (hyperCalcemia, Renal failure, Anemia, and Bone lesion), which profoundly affect both the Health-Related Quality of Life (HRQoL) and the life expectancy of patients. Despite all enhancement and improvement in therapeutic strategies, MM is almost incurable, and patients suffering from this disease eventually relapse. Curcumin is an active and non-toxic phenolic compound, isolated from the rhizome of Curcuma longa L. It has been widely studied and has a confirmed broad range of therapeutic properties, especially anti-cancer activity, and others, including anti-proliferation, anti-angiogenesis, antioxidant and anti-mutation activities. Curcumin induces apoptosis in cancerous cells and prevents Multidrug Resistance (MDR). Growing evidence concerning the therapeutic properties of curcumin caused a pharmacological impact on MM. It is confirmed that curcumin interferes with various signaling pathways and cell cycle checkpoints, and with oncogenes. In this paper, we summarized the anti- MM effects of curcumin.
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Affiliation(s)
- Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hossein Bagheri
- Molecular and Medicine Research Center, Department of Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Faezeh Ghasemi
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Next to Milad Tower, Tehran, Iran
| | | | | | - Yvan V Heyden
- Department of Analytical Chemistry, Applied Chemometrics and Molecular Modelling, Vrije Universiteit Brussel (VUB), Brussels, Belgium
| | - Erfan Mortezapour
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Ali Nikdasti
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Philippe Jeandet
- Research Unit, Induced Resistance and Plant Bioprotection, EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, University of Reims Champagne-Ardenne, PO Box 1039, 51687 Reims Cedex 2, France
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, 23200, Pakistan
| | - Amirhossein Sahebkar
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Song Y, Wang X, Wang F, Peng X, Li P, Liu S, Zhang D. Identification of four genes and biological characteristics of esophageal squamous cell carcinoma by integrated bioinformatics analysis. Cancer Cell Int 2021; 21:123. [PMID: 33602210 PMCID: PMC7890804 DOI: 10.1186/s12935-021-01814-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 02/06/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) has become one of the most serious diseases affecting populations worldwide and is the primary subtype of esophageal cancer (EC). However, the molecular mechanisms governing the development of ESCC have not been fully elucidated. METHODS The robust rank aggregation method was performed to identify the differentially expressed genes (DEGs) in six datasets (GSE17351, GSE20347, GSE23400, GSE26886, GSE38129 and GSE77861) from the Gene Expression Omnibus (GEO). The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to extract four hub genes from the protein-protein interaction (PPI) network. Module analysis and disease free survival analysis of the four hub genes were performed by Cytoscape and GEPIA. The expression of hub genes was analyzed by GEPIA and the Oncomine database and verified by real-time quantitative PCR (qRT-PCR). RESULTS In total, 720 DEGs were identified in the present study; these genes consisted of 302 upregulated genes and 418 downregulated genes that were significantly enriched in the cellular component of the extracellular matrix part followed by the biological process of the cell cycle phase and nuclear division. The primary enriched pathways were hsa04110:Cell cycle and hsa03030:DNA replication. Four hub genes were screened out, namely, SPP1, MMP12, COL10A1 and COL5A2. These hub genes all exhibited notably increased expression in ESCC samples compared with normal samples, and ESCC patients with upregulation of all four hub genes exhibited worse disease free survival. CONCLUSIONS SPP1, MMP12, COL10A1 and COL5A2 may participate in the tumorigenesis of ESCC and demonstrate the potential to serve as molecular biomarkers in the early diagnosis of ESCC. This study may help to elucidate the molecular mechanisms governing ESCC and facilitate the selection of targets for early treatment and diagnosis.
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Affiliation(s)
- Yexun Song
- Department of Otolaryngology-Head Neck Surgery, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.,Department of Otolaryngology-Head Neck Surgery, The Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China
| | - Xianyao Wang
- Department of Otolaryngology-Head Neck Surgery, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.,Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China
| | - Fengjun Wang
- Department of Otolaryngology-Head Neck Surgery, The Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China
| | - Xiaowei Peng
- Department of Oncology Plastic Surgery, Hunan Province Cancer Hospital, Changsha, 410007, Hunan, China
| | - Peiyu Li
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.,Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, 410013, Hunan, China
| | - Shaojun Liu
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.,Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, 410013, Hunan, China
| | - Decai Zhang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China. .,Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, 410013, Hunan, China.
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Tamtaji OR, Hadinezhad T, Fallah M, Shahmirzadi AR, Taghizadeh M, Behnam M, Asemi Z. The Therapeutic Potential of Quercetin in Parkinson's Disease: Insights into its Molecular and Cellular Regulation. Curr Drug Targets 2021; 21:509-518. [PMID: 31721700 DOI: 10.2174/1389450120666191112155654] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Revised: 09/30/2019] [Accepted: 10/08/2019] [Indexed: 12/13/2022]
Abstract
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNc). PD is a multifactorial disorder, with several different factors being suggested to play a synergistic pathophysiological role, including oxidative stress, autophagy, underlying pro-inflammatory events and neurotransmitters abnormalities. Overall, PD can be viewed as the product of a complex interaction of environmental factors acting on a given genetic background. The importance of this subject has gained more attention to discover novel therapies to prevent as well as treat PD. According to previous research, drugs used to treat PD have indicated significant limitations. Therefore, the role of flavonoids has been extensively studied in PD treatment. Quercetin, a plant flavonol from the flavonoid group, has been considered as a supplemental therapy for PD. Quercetin has pharmacological functions in PD by controlling different molecular pathways. Although few studies intended to evaluate the basis for the use of quercetin in the context of PD have been conducted so far, at present, there is very little evidence available addressing the underlying mechanisms of action. Various principal aspects of these treatment procedures remain unknown. Here, currently existing knowledge supporting the use of quercetin for the clinical management of PD has been reviewed.
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Affiliation(s)
- Omid Reza Tamtaji
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Tooba Hadinezhad
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Maryam Fallah
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Mohsen Taghizadeh
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
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Cold atmospheric plasma induced genotoxicity and cytotoxicity in esophageal cancer cells. Mol Biol Rep 2021; 48:1323-1333. [PMID: 33547994 DOI: 10.1007/s11033-021-06178-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 01/20/2021] [Indexed: 12/11/2022]
Abstract
In this paper, we studied the functional effects of cold atmospheric plasma (CAP) on the esophageal cancer cell line (KYSE-30) by direct and indirect treatment and fibroblast cell lines as normal cells. KYSE-30 cells were treated with CAP at different time points of 60, 90, 120 and, 240 s for direct exposure and 90, 180, 240 and, 360 s for indirect exposure. Cell viability was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and apoptosis induction in the treated cells was measured by Annexin-V/PI using flow cytometry. The expression of apoptotic related genes (BAX/BCL-2) was analyzed by real-time polymerase chain reaction. Moreover, the genotoxicity was analyzed by comet assay. Cell viability results showed that direct CAP treatment has a markedly cytotoxic impact on the reduction of KYSE-30 cells at 60 s (p = 0.000), while indirect exposure was less impactful (p > 0.05). The results of the Annexin-V/PI staining confirmed this analysis. Subsequently, the genotoxicity study of the direct CAP treatment demonstrated a longer tail-DNA length and caused increase in DNA damage in the cells (p < 0.00001) as well as shift BAX/BCL-2 toward apoptosis. The concentration of H2O2 and NO2- in direct CAP treatment was significantly higher than indirect (p > 0.05). Treatment with direct CAP showed genotoxicity in cancer cells. Collectively, our results pave a deeper understanding of CAP functions and the way for further investigations in the field of esophageal cancer treatment.
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Shabbir U, Rubab M, Daliri EBM, Chelliah R, Javed A, Oh DH. Curcumin, Quercetin, Catechins and Metabolic Diseases: The Role of Gut Microbiota. Nutrients 2021; 13:206. [PMID: 33445760 PMCID: PMC7828240 DOI: 10.3390/nu13010206] [Citation(s) in RCA: 167] [Impact Index Per Article: 41.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/07/2021] [Accepted: 01/08/2021] [Indexed: 02/07/2023] Open
Abstract
Polyphenols (PPs) are the naturally occurring bioactive components in fruits and vegetables, and they are the most abundant antioxidant in the human diet. Studies are suggesting that ingestion of PPs might be helpful to ameliorate metabolic syndromes that may contribute in the prevention of several chronic disorders like diabetes, obesity, hypertension, and colon cancer. PPs have structural diversity which impacts their bioavailability as they accumulate in the large intestine and are extensively metabolized through gut microbiota (GM). Intestinal microbiota transforms PPs into their metabolites to make them bioactive. Interestingly, not only GM act on PPs to metabolize them but PPs also modulate the composition of GM. Thus, change in GM from pathogenic to beneficial ones may be helpful to ameliorate gut health and associated diseases. However, to overcome the low bioavailability of PPs, various approaches have been developed to improve their solubility and transportation through the gut. In this review, we present evidence supporting the structural changes that occur after metabolic reactions in PPs (curcumin, quercetin, and catechins) and their effect on GM composition that leads to improving overall gut health and helping to ameliorate metabolic disorders.
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Affiliation(s)
- Umair Shabbir
- Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon 24341, Korea; (U.S.); (M.R.); (E.B.-M.D.); (R.C.)
| | - Momna Rubab
- Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon 24341, Korea; (U.S.); (M.R.); (E.B.-M.D.); (R.C.)
| | - Eric Banan-Mwine Daliri
- Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon 24341, Korea; (U.S.); (M.R.); (E.B.-M.D.); (R.C.)
| | - Ramachandran Chelliah
- Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon 24341, Korea; (U.S.); (M.R.); (E.B.-M.D.); (R.C.)
| | - Ahsan Javed
- Department of Food Science & Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University, Daegu 41566, Korea;
| | - Deog-Hwan Oh
- Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon 24341, Korea; (U.S.); (M.R.); (E.B.-M.D.); (R.C.)
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Curcumin and Its Derivatives as Theranostic Agents in Alzheimer's Disease: The Implication of Nanotechnology. Int J Mol Sci 2020; 22:ijms22010196. [PMID: 33375513 PMCID: PMC7795367 DOI: 10.3390/ijms22010196] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/15/2020] [Accepted: 12/24/2020] [Indexed: 02/07/2023] Open
Abstract
Curcumin is a polyphenolic natural compound with diverse and attractive biological properties, which may prevent or ameliorate pathological processes underlying age-related cognitive decline, Alzheimer's disease (AD), dementia, or mode disorders. AD is a chronic neurodegenerative disorder that is known as one of the rapidly growing diseases, especially in the elderly population. Moreover, being the eminent cause of dementia, posing problems for families, societies as well a severe burden on the economy. There are no effective drugs to cure AD. Although curcumin and its derivatives have shown properties that can be considered useful in inhibiting the hallmarks of AD, however, they have low bioavailability. Furthermore, to combat diagnostic and therapeutic limitations, various nanoformulations have also been recognized as theranostic agents that can also enhance the pharmacokinetic properties of curcumin and other bioactive compounds. Nanocarriers have shown beneficial properties to deliver curcumin and other nutritional compounds against the blood-brain barrier to efficiently distribute them in the brain. This review spotlights the role and effectiveness of curcumin and its derivatives in AD. Besides, the gut metabolism of curcumin and the effects of nanoparticles and their possible activity as diagnostic and therapeutic agents in AD also discussed.
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Zhao Q, Guo J, Zhao Y, Shen J, Kaboli PJ, Xiang S, Du F, Wu X, Li M, Wan L, Li X, Wen Q, Li J, Zou C, Xiao Z. Comprehensive assessment of PD-L1 and PD-L2 dysregulation in gastrointestinal cancers. Epigenomics 2020; 12:2155-2171. [PMID: 33337915 DOI: 10.2217/epi-2020-0093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background: PD-L1 and PD-L2 are ligands of PD-1. Their overexpression has been reported in different cancers. However, the underlying mechanism of PD-L1 and PD-L2 dysregulation and their related signaling pathways are still unclear in gastrointestinal cancers. Materials & methods: The expression of PD-L1 and PD-L2 were studied in The Cancer Genome Atlas and Genotype-Tissue Expression databases. The gene and protein alteration of PD-L1 and PD-L2 were analyzed in cBioportal. The direct transcription factor regulating PD-L1/PD-L2 was determined with ChIP-seq data. The association of PD-L1/PD-L2 expression with clinicopathological parameters, survival, immune infiltration and tumor mutation burden were investigated with data from The Cancer Genome Atlas. Potential targets and pathways of PD-L1 and PD-L2 were determined by protein enrichment, WebGestalt and gene ontology. Results: Comprehensive analysis revealed that PD-L1 and PD-L2 were significantly upregulated in most types of gastrointestinal cancers and their expressions were positively correlated. SP1 was a key transcription factor regulating the expression of PD-L1. Conclusion: Higher PD-L1 or PD-L2 expression was significantly associated with poor overall survival, higher tumor mutation burden and more immune and stromal cell populations. Finally, HIF-1, ERBB and mTOR signaling pathways were most significantly affected by PD-L1 and PD-L2 dysregulation. Altogether, this study provided comprehensive analysis of the dysregulation of PD-L1 and PD-L2, its underlying mechanism and downstream pathways, which add to the knowledge of manipulating PD-L1/PD-L2 for cancer immunotherapy.
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Affiliation(s)
- Qijie Zhao
- Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, PR China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China.,Department of Pathophysiology, College of Basic Medical Science, Southwest Medical University, Luzhou 646000, Sichuan, PR China
| | - Jinan Guo
- The department of urology, The Second Clinical Medical college of Jinan University (Shenzhen people's Hospital), The First Affiliated Hospital of South University of Science & Technology of China, Shenzhen Urology Minimally Invasive Engineering Center, Shenzhen, Guangdong, PR China.,Shenzhen Public Service Platform on Tumor Precision Medicine & Molecular Diagnosis, Shenzhen, Guangdong, PR China
| | - Yueshui Zhao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China.,South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, PR China
| | - Jing Shen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China.,South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, PR China
| | - Parham Jabbarzadeh Kaboli
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China.,South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, PR China
| | - Shixin Xiang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China
| | - Fukuan Du
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China.,South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, PR China
| | - Xu Wu
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China.,South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, PR China
| | - Mingxing Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China.,South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, PR China
| | - Lin Wan
- Department of Hematology & Oncology, The Children's Hospital of Soochow, Jiangsu, PR China
| | - Xiang Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China
| | - Qinglian Wen
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China
| | - Jing Li
- Department of Oncology & Hematology, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, Sichuan, PR China
| | - Chang Zou
- Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, PR China.,Shenzhen Public Service Platform on Tumor Precision Medicine & Molecular Diagnosis, Shenzhen, Guangdong, PR China
| | - Zhangang Xiao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China.,South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, PR China
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Zhang N, Shi J, Shi X, Chen W, Liu J. Mutational Characterization and Potential Prognostic Biomarkers of Chinese Patients with Esophageal Squamous Cell Carcinoma. Onco Targets Ther 2020; 13:12797-12809. [PMID: 33363385 PMCID: PMC7751839 DOI: 10.2147/ott.s275688] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 11/12/2020] [Indexed: 12/11/2022] Open
Abstract
Purpose Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China and the 5-year mortality rate is up to 70%. Studies on the ESCC genetic landscape are needed to further explore clinical therapeutic strategies. In this study, we evaluated the genetic landscape of ESCC to aid the search for clinical therapeutic strategies. Patients and Methods A total of 225 ESCC patients were enrolled in this study. Deep sequencing of 450 cancer genes was performed on formalin-fixed paraffin-embedded tumor biopsies and matched blood samples from patients. Tumor mutational burden (TMB) was calculated using an algorithm developed in-house. Results Our results showed that the most commonly mutated genes in ESCC were TP53 (96%), CCND1 (46%), FGF4 (44%), FGF19 (44%), FGF3 (44%), CDKN2A (31%), PIK3CA (26%), NOTCH1 (24%), KMT2D (18%), FAT1 (16%), and LRP1B (16%). We found that TMB correlated with patient drinking status. We identified mutations associated with sex, early ESCC, high TMB, and metastasis lymph nodes. KMT2D mutations associated with sex (P = 0.035), tumor stage (P = 0.016), high TMB (P = 0.0072), and overall survival of patients (P = 0.0026). SPEN mutations associated with high TMB (P = 0.0016) and metastasis-positive lymph nodes (P = 0.027). These results suggested that SPEN and KMT2D could be potential prognosis biomarkers for Chinese patients with ESCC. We also found that the number of positive lymph nodes was associated with disease-free survival. Clinical target gene analysis indicated that nearly half of Chinese ESCC patients might benefit from treatment with gene-specific target drugs. Conclusion Our study revealed the ESCC mutational landscape in 225 Chinese patients and uncovered the potential prognosis biomarker for Chinese patients with ESCC.
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Affiliation(s)
- Nan Zhang
- Department of Thoracic Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
| | - Junping Shi
- Department of Medicine, OrigiMed Co. Ltd, Shanghai, People's Republic of China
| | - Xiaoliang Shi
- Department of Medicine, OrigiMed Co. Ltd, Shanghai, People's Republic of China
| | - Wenting Chen
- Department of Medicine, OrigiMed Co. Ltd, Shanghai, People's Republic of China
| | - Junfeng Liu
- Department of Thoracic Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
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Ashrafizadeh M, Zarrabi A, Hushmandi K, Zarrin V, Moghadam ER, Hashemi F, Makvandi P, Samarghandian S, Khan H, Hashemi F, Najafi M, Mirzaei H. Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review. Front Pharmacol 2020; 11:585413. [PMID: 33381035 PMCID: PMC7767860 DOI: 10.3389/fphar.2020.585413] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/12/2020] [Indexed: 12/11/2022] Open
Abstract
Immune response, proliferation, migration and angiogenesis are juts a few of cellular events that are regulated by transforming growth factor-β (TGF-β) in cells. A number of studies have documented that TGF-β undergoes abnormal expression in different diseases, e.g., diabetes, cancer, fibrosis, asthma, arthritis, among others. This has led to great fascination into this signaling pathway and developing agents with modulatory impact on TGF-β. Curcumin, a natural-based compound, is obtained from rhizome and roots of turmeric plant. It has a number of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-diabetes and so on. Noteworthy, it has been demonstrated that curcumin affects different molecular signaling pathways such as Wnt/β-catenin, Nrf2, AMPK, mitogen-activated protein kinase and so on. In the present review, we evaluate the potential of curcumin in regulation of TGF-β signaling pathway to corelate it with therapeutic impacts of curcumin. By modulation of TGF-β (both upregulation and down-regulation), curcumin ameliorates fibrosis, neurological disorders, liver disease, diabetes and asthma. Besides, curcumin targets TGF-β signaling pathway which is capable of suppressing proliferation of tumor cells and invading cancer cells.
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Affiliation(s)
- Milad Ashrafizadeh
- Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Istanbul, Turkey
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Istanbul, Turkey
| | - Ali Zarrabi
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Istanbul, Turkey
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Vahideh Zarrin
- Laboratory for Stem Cell Research, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ebrahim Rahmani Moghadam
- Department of Anatomical Sciences, School of Medicine, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Pooyan Makvandi
- Centre for Micro-BioRobotics, Istituto Italiano di Tecnologia, Pisa, Italy
| | | | - Haroon Khan
- Student Research Committee, Department of Physiotherapy, Faculty of Rehabilitation, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Fardin Hashemi
- Medical Technology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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50
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Hackman GL, Collins M, Lu X, Lodi A, DiGiovanni J, Tiziani S. Predicting and Quantifying Antagonistic Effects of Natural Compounds Given with Chemotherapeutic Agents: Applications for High-Throughput Screening. Cancers (Basel) 2020; 12:cancers12123714. [PMID: 33322034 PMCID: PMC7763027 DOI: 10.3390/cancers12123714] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 12/04/2020] [Accepted: 12/09/2020] [Indexed: 01/12/2023] Open
Abstract
Natural products have been used for centuries to treat various human ailments. In recent decades, multi-drug combinations that utilize natural products to synergistically enhance the therapeutic effects of cancer drugs have been identified and have shown success in improving treatment outcomes. While drug synergy research is a burgeoning field, there are disagreements on the definitions and mathematical parameters that prevent the standardization and proper usage of the terms synergy, antagonism, and additivity. This contributes to the relatively small amount of data on the antagonistic effects of natural products on cancer drugs that can diminish their therapeutic efficacy and prevent cancer regression. The ability of natural products to potentially degrade or reverse the molecular activity of cancer therapeutics represents an important but highly under-emphasized area of research that is often overlooked in both pre-clinical and clinical studies. This review aims to evaluate the body of work surrounding the antagonistic interactions between natural products and cancer therapeutics and highlight applications for high-throughput screening (HTS) and deep learning techniques for the identification of natural products that antagonize cancer drug efficacy.
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Affiliation(s)
- G. Lavender Hackman
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712, USA; (G.L.H.); (M.C.); (X.L.); (A.L.)
- Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX 78723, USA;
| | - Meghan Collins
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712, USA; (G.L.H.); (M.C.); (X.L.); (A.L.)
- Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX 78723, USA;
| | - Xiyuan Lu
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712, USA; (G.L.H.); (M.C.); (X.L.); (A.L.)
- Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX 78723, USA;
| | - Alessia Lodi
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712, USA; (G.L.H.); (M.C.); (X.L.); (A.L.)
- Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX 78723, USA;
| | - John DiGiovanni
- Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX 78723, USA;
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA
| | - Stefano Tiziani
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712, USA; (G.L.H.); (M.C.); (X.L.); (A.L.)
- Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX 78723, USA;
- Department of Oncology, Dell Medical School, LiveSTRONG Cancer Institutes, The University of Texas at Austin, Austin, TX 78723, USA
- Correspondence: ; Tel.: +1-512-495-4706
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