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Kaya Çakir H, Eroğlu O. Investigation of the synergic effect of mocetinostat and capecitabine in a triple-negative breast neoplasms mouse model. J Investig Med 2025; 73:320-327. [PMID: 39690705 DOI: 10.1177/10815589241309603] [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] [Indexed: 12/19/2024]
Abstract
Combined administration of two or more drugs is emerging as a new strategy in triple-negative breast neoplasms. This is the first study to investigate the combination of the histone deacetylase inhibitor mocetinostat and the antimetabolite drug capecitabine in triple-negative mammary neoplasms in a preclinical mouse model. Thirty-five female mice were grouped into the control group, capecitabine group, mocetinostat group, and combined drugs group. At the end of the experimental period, body weight, and tumor weight were measured and tumor tissue and lung tissue were histologically examined. The results showed that the body weight of mice in the drug-treated groups was reduced by about 18%. Tumor weights were also reduced by 21% in the mocetinostat group, 27.5% in the capecitabine group, and 45% in the combined group. The combination of mocetinostat and capecitabine decreased the formation of tumors and metastases in lung tissue. In summary, the combination of mocetinostat and capecitabine was more effective than either drug alone in reducing the size of triple-negative breast neoplasms in a mouse model.
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Affiliation(s)
- Hacer Kaya Çakir
- Department of Molecular Biology and Genetics, Faculty of Science, Bilecik Seyh Edebali University, Bilecik, Turkey
| | - Onur Eroğlu
- Department of Molecular Biology and Genetics, Faculty of Science, Bilecik Seyh Edebali University, Bilecik, Turkey
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2
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Fernandez-Muñoz KV, Sánchez-Barrera CÁ, Meraz-Ríos M, Reyes JL, Pérez-Yépez EA, Ortiz-Melo MT, Terrazas LI, Mendoza-Rodriguez MG. Natural Alternatives in the Treatment of Colorectal Cancer: A Mechanisms Perspective. Biomolecules 2025; 15:326. [PMID: 40149862 PMCID: PMC11940303 DOI: 10.3390/biom15030326] [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: 01/24/2025] [Revised: 02/16/2025] [Accepted: 02/19/2025] [Indexed: 03/29/2025] Open
Abstract
Colorectal cancer (CRC) is one of the deadliest neoplasia. Intrinsic or acquired resistance is the main cause of failure of therapy regimens that leads to relapse and death in CRC patients. The widely used chemotherapeutic agent 5-fluorouracil (5-FU) remains the mainstay for therapeutic combinations. Unfortunately, chemotherapeutic resistance and side effects are frequent events that compromise the success of these therapies; the dysregulation of enzymes that regulate 5-FU metabolism increases the expression and activity of efflux pumps. Additional tumor cell adaptations such as epithelial-mesenchymal transition (EMT), autophagy shaping of the tumor microenvironment, and inflammation contribute to chemoresistance. Finding new strategies and alternatives to enhance conventional chemotherapies has become necessary. Recently, the study of natural compounds has been gaining strength as an alternative to chemotherapeutics in different cancers. Curcumin, trimethylglycine, resveratrol, artemisinin, and some helminth-derived molecules, among others, are some natural compounds studied in the context of CRC. This review discusses the main benefits, mechanisms, advances, and dark side of conventional chemotherapeutics currently evaluated in CRC treatment. We also analyzed the landscape of alternative non-conventional compounds and their underlying mechanisms of action, which could, in the short term, provide fundamental knowledge to harness their anti-tumor effects and allow them to be used as alternative adjuvant therapies.
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Affiliation(s)
- Karen Vanessa Fernandez-Muñoz
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico; (K.V.F.-M.); (C.Á.S.-B.); (M.T.O.-M.)
- Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, Ciudad de México 07360, Mexico
| | - Cuauhtémoc Ángel Sánchez-Barrera
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico; (K.V.F.-M.); (C.Á.S.-B.); (M.T.O.-M.)
| | - Marco Meraz-Ríos
- Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, Ciudad de México 07360, Mexico
| | - Jose Luis Reyes
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico; (K.V.F.-M.); (C.Á.S.-B.); (M.T.O.-M.)
| | | | - Maria Teresa Ortiz-Melo
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico; (K.V.F.-M.); (C.Á.S.-B.); (M.T.O.-M.)
| | - Luis I. Terrazas
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico; (K.V.F.-M.); (C.Á.S.-B.); (M.T.O.-M.)
- Laboratorio Nacional en Salud, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico
| | - Monica Graciela Mendoza-Rodriguez
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico; (K.V.F.-M.); (C.Á.S.-B.); (M.T.O.-M.)
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Aleksandrova Y, Neganova M. Antioxidant Senotherapy by Natural Compounds: A Beneficial Partner in Cancer Treatment. Antioxidants (Basel) 2025; 14:199. [PMID: 40002385 PMCID: PMC11851806 DOI: 10.3390/antiox14020199] [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: 01/30/2025] [Revised: 02/06/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Aging is a general biological process inherent in all living organisms. It is characterized by progressive cellular dysfunction. For many years, aging has been widely recognized as a highly effective mechanism for suppressing the progression of malignant neoplasms. However, in recent years, increasing evidence suggests a "double-edged" role of aging in cancer development. According to these data, aging is not only a tumor suppressor that leads to cell cycle arrest in neoplastic cells, but also a cancer promoter that ensures a chronic proinflammatory and immunosuppressive microenvironment. In this regard, in our review, we discuss recent data on the destructive role of senescent cells in the pathogenesis of cancer. We also identify for the first time correlations between the modulation of the senescence-associated secretory phenotype and the antitumor effects of naturally occurring molecules.
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Affiliation(s)
| | - Margarita Neganova
- Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St. 28, Bld. 1, Moscow 119991, Russia;
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4
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Shadnoush M, Momenan M, Seidel V, Tierling S, Fatemi N, Nazemalhosseini-Mojarad E, Norooz MT, Cheraghpour M. A comprehensive update on the potential of curcumin to enhance chemosensitivity in colorectal cancer. Pharmacol Rep 2025; 77:103-123. [PMID: 39304638 DOI: 10.1007/s43440-024-00652-y] [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: 01/15/2024] [Revised: 09/07/2024] [Accepted: 09/09/2024] [Indexed: 09/22/2024]
Abstract
Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer-related mortality worldwide. The efficacy of chemotherapy agents in CRC treatment is often limited due to toxic side effects, heterogeneity of cancer cells, and the possibility of chemoresistance which promotes cancer cell survival through several mechanisms. Combining chemotherapy agents with natural compounds like curcumin, a polyphenol compound from the Curcuma longa plant, has been reported to overcome chemoresistance and increase the sensitivity of cancer cells to chemotherapeutics. Curcumin, alone or in combination with chemotherapy agents, has been demonstrated to prevent chemoresistance by modulating various signaling pathways, reducing the expression of drug resistance-related genes. The purpose of this article is to provide a comprehensive update on studies that have investigated the ability of curcumin to enhance the efficacy of chemotherapy agents used in CRC. It is hoped that it can serve as a template for future research on the efficacy of curcumin, or other natural compounds, combined with chemotherapy agents to maximize the effectiveness of therapy and reduce the side effects that occur in CRC or other cancers.
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Affiliation(s)
- Mahdi Shadnoush
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O.Box, Tehran, 16635-148, Iran
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehrnaz Momenan
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Veronique Seidel
- Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
| | - Sascha Tierling
- Department of Genetics/Epigenetics, Faculty NT, Life Sciences, Saarland University, Saarbrücken, Germany
| | - Nayeralsadat Fatemi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O.Box, Tehran, 16635-148, Iran
| | - Ehsan Nazemalhosseini-Mojarad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Tayefeh Norooz
- General Surgery Department, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O.Box, Tehran, 16635-148, Iran.
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Shoari A, Ashja Ardalan A, Dimesa AM, Coban MA. Targeting Invasion: The Role of MMP-2 and MMP-9 Inhibition in Colorectal Cancer Therapy. Biomolecules 2024; 15:35. [PMID: 39858430 PMCID: PMC11762759 DOI: 10.3390/biom15010035] [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: 12/09/2024] [Revised: 12/27/2024] [Accepted: 12/29/2024] [Indexed: 01/27/2025] Open
Abstract
Colorectal cancer (CRC) remains one of the most prevalent and lethal cancers worldwide, prompting ongoing research into innovative therapeutic strategies. This review aims to systematically evaluate the role of gelatinases, specifically MMP-2 and MMP-9, as therapeutic targets in CRC, providing a critical analysis of their potential to improve patient outcomes. Gelatinases, specifically MMP-2 and MMP-9, play critical roles in the processes of tumor growth, invasion, and metastasis. Their expression and activity are significantly elevated in CRC, correlating with poor prognosis and lower survival rates. This review provides a comprehensive overview of the pathophysiological roles of gelatinases in CRC, highlighting their contribution to tumor microenvironment modulation, angiogenesis, and the metastatic cascade. We also critically evaluate recent advancements in the development of gelatinase inhibitors, including small molecule inhibitors, natural compounds, and novel therapeutic approaches like gene silencing techniques. Challenges such as nonspecificity, adverse side effects, and resistance mechanisms are discussed. We explore the potential of gelatinase inhibition in combination therapies, particularly with conventional chemotherapy and emerging targeted treatments, to enhance therapeutic efficacy and overcome resistance. The novelty of this review lies in its integration of recent findings on diverse inhibition strategies with insights into their clinical relevance, offering a roadmap for future research. By addressing the limitations of current approaches and proposing novel strategies, this review underscores the potential of gelatinase inhibitors in CRC prevention and therapy, inspiring further exploration in this promising area of oncological treatment.
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Affiliation(s)
- Alireza Shoari
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Arghavan Ashja Ardalan
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy;
| | | | - Mathew A. Coban
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA;
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Amaroli A, Panfoli I, Bozzo M, Ferrando S, Candiani S, Ravera S. The Bright Side of Curcumin: A Narrative Review of Its Therapeutic Potential in Cancer Management. Cancers (Basel) 2024; 16:2580. [PMID: 39061221 PMCID: PMC11275093 DOI: 10.3390/cancers16142580] [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: 06/18/2024] [Revised: 07/11/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
Curcumin, a polyphenolic compound derived from Curcuma longa, exhibits significant therapeutic potential in cancer management. This review explores curcumin's mechanisms of action, the challenges related to its bioavailability, and its enhancement through modern technology and approaches. Curcumin demonstrates strong antioxidant and anti-inflammatory properties, contributing to its ability to neutralize free radicals and inhibit inflammatory mediators. Its anticancer effects are mediated by inducing apoptosis, inhibiting cell proliferation, and interfering with tumor growth pathways in various colon, pancreatic, and breast cancers. However, its clinical application is limited by its poor bioavailability due to its rapid metabolism and low absorption. Novel delivery systems, such as curcumin-loaded hydrogels and nanoparticles, have shown promise in improving curcumin bioavailability and therapeutic efficacy. Additionally, photodynamic therapy has emerged as a complementary approach, where light exposure enhances curcumin's anticancer effects by modulating molecular pathways crucial for tumor cell growth and survival. Studies highlight that combining low concentrations of curcumin with visible light irradiation significantly boosts its antitumor efficacy compared to curcumin alone. The interaction of curcumin with cytochromes or drug transporters may play a crucial role in altering the pharmacokinetics of conventional medications, which necessitates careful consideration in clinical settings. Future research should focus on optimizing delivery mechanisms and understanding curcumin's pharmacokinetics to fully harness its therapeutic potential in cancer treatment.
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Affiliation(s)
- Andrea Amaroli
- BIO-Photonics Overarching Research Laboratory (BIOPHOR), Department of Earth, Environmental and Life Sciences (DISTAV), University of Genoa, 16132 Genoa, Italy; (M.B.); (S.F.); (S.C.)
| | - Isabella Panfoli
- Department of Pharmacy (DIFAR), University of Genoa, 16132 Genoa, Italy;
| | - Matteo Bozzo
- BIO-Photonics Overarching Research Laboratory (BIOPHOR), Department of Earth, Environmental and Life Sciences (DISTAV), University of Genoa, 16132 Genoa, Italy; (M.B.); (S.F.); (S.C.)
| | - Sara Ferrando
- BIO-Photonics Overarching Research Laboratory (BIOPHOR), Department of Earth, Environmental and Life Sciences (DISTAV), University of Genoa, 16132 Genoa, Italy; (M.B.); (S.F.); (S.C.)
| | - Simona Candiani
- BIO-Photonics Overarching Research Laboratory (BIOPHOR), Department of Earth, Environmental and Life Sciences (DISTAV), University of Genoa, 16132 Genoa, Italy; (M.B.); (S.F.); (S.C.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Silvia Ravera
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
- Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genoa, Italy
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7
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Choudhury SD, Kumar P, Choudhury D. Bioactive nutraceuticals as G4 stabilizers: potential cancer prevention and therapy-a critical review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:3585-3616. [PMID: 38019298 DOI: 10.1007/s00210-023-02857-z] [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: 08/14/2023] [Accepted: 11/13/2023] [Indexed: 11/30/2023]
Abstract
G-quadruplexes (G4) are non-canonical, four-stranded, nucleic acid secondary structures formed in the guanine-rich sequences, where guanine nucleotides associate with each other via Hoogsteen hydrogen bonding. These structures are widely found near the functional regions of the mammalian genome, such as telomeres, oncogenic promoters, and replication origins, and play crucial regulatory roles in replication and transcription. Destabilization of G4 by various carcinogenic agents allows oncogene overexpression and extension of telomeric ends resulting in dysregulation of cellular growth-promoting oncogenesis. Therefore, targeting and stabilizing these G4 structures with potential ligands could aid cancer prevention and therapy. The field of G-quadruplex targeting is relatively nascent, although many articles have demonstrated the effect of G4 stabilization on oncogenic expressions; however, no previous study has provided a comprehensive analysis about the potency of a wide variety of nutraceuticals and some of their derivatives in targeting G4 and the lattice of oncogenic cell signaling cascade affected by them. In this review, we have discussed bioactive G4-stabilizing nutraceuticals, their sources, mode of action, and their influence on cellular signaling, and we believe our insight would bring new light to the current status of the field and motivate researchers to explore this relatively poorly studied arena.
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Affiliation(s)
- Satabdi Datta Choudhury
- Department of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala, Punjab, 147004, India
| | - Prateek Kumar
- School of Basic Sciences, Indian Institute of Technology (IIT), Mandi, Himachal Pradesh, 175005, India
| | - Diptiman Choudhury
- Department of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala, Punjab, 147004, India.
- Centre for Excellence in Emerging Materials, Thapar Institute of Engineering and Technology, Patiala, Punjab, 147004, India.
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Campanelli G, Deabel RA, Puaar A, Devarakonda LS, Parupathi P, Zhang J, Waxner N, Yang C, Kumar A, Levenson AS. Molecular Efficacy of Gnetin C as Dual-Targeted Therapy for Castrate-Resistant Prostate Cancer. Mol Nutr Food Res 2023; 67:e2300479. [PMID: 37863824 DOI: 10.1002/mnfr.202300479] [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: 07/10/2023] [Revised: 08/29/2023] [Indexed: 10/22/2023]
Abstract
SCOPE Resistance of castrate-resistant prostate cancer (CRPC) to enzalutamide (Enz) involves the expression of constitutively active androgen receptor splice variant (AR-V7). In addition to altered AR pathways, CRPC is characterized by "non-AR-driven" signaling, which includes an overexpression of metastasis-associated protein 1 (MTA1). Combining natural compounds with anticancer drugs may enhance drug effectiveness while reducing adverse effects. In this study, the in vitro and in vivo anticancer effects of Gnetin C (GnC) alone and in combination with Enz against CRPC are examined. METHODS AND RESULTS The effects of GnC alone and in combination with Enz are assessed by cell viability, clonogenic survival, cell migration, and AR and MTA1 expression using 22Rv1 cells. The tumor growth in vivo is assessed by bioluminescent imaging, western blots, RT-PCR, and IHC. GnC alone and in combined treatment inhibit cell viability, clonogenic survival and migration, and AR and MTA1 expression in 22Rv1 cells. The underlying AR- and MTA1-targeted anticancer mechanisms of treatments in vivo involve inhibition of proliferation and angiogenesis, and induction of apoptosis. CONCLUSION The findings demonstrate that GnC alone and GnC combined with Enz effectively inhibits AR- and MTA1-promoted tumor-progression in advanced CRPC, which indicates its potential as a novel therapeutic approach for CRPC.
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Affiliation(s)
- Gisella Campanelli
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| | - Rabab Al Deabel
- School of Health Professions and Nursing, Long Island University, Brookville, NY, USA
| | - Anand Puaar
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| | | | - Prashanth Parupathi
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| | | | - Noah Waxner
- College of Veterinary Medicine, Long Island University, Brookville, NY, USA
| | - Ching Yang
- College of Veterinary Medicine, Long Island University, Brookville, NY, USA
| | - Avinash Kumar
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| | - Anait S Levenson
- College of Veterinary Medicine, Long Island University, Brookville, NY, USA
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Hjazi A, Nasir F, Noor R, Alsalamy A, Zabibah RS, Romero-Parra RM, Ullah MI, Mustafa YF, Qasim MT, Akram SV. The pathological role of C-X-C chemokine receptor type 4 (CXCR4) in colorectal cancer (CRC) progression; special focus on molecular mechanisms and possible therapeutics. Pathol Res Pract 2023; 248:154616. [PMID: 37379710 DOI: 10.1016/j.prp.2023.154616] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/07/2023] [Accepted: 06/10/2023] [Indexed: 06/30/2023]
Abstract
Colorectal cancer (CRC) is comprised of transformed cells and non-malignant cells including cancer-associated fibroblasts (CAF), endothelial vasculature cells, and tumor-infiltrating cells. These nonmalignant cells, as well as soluble factors (e.g., cytokines), and the extracellular matrix (ECM), form the tumor microenvironment (TME). In general, the cancer cells and their surrounding TME can crosstalk by direct cell-to-cell contact and via soluble factors, such as cytokines (e.g., chemokines). TME not only promotes cancer progression through growth-promoting cytokines but also provides resistance to chemotherapy. Understanding the mechanisms of tumor growth and progression and the roles of chemokines in CRC will likely suggest new therapeutic targets. In this line, a plethora of reports has evidenced the critical role of chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12 or SDF-1) axis in CRC pathogenesis. In the current review, we take a glimpse into the role of the CXCR4/CXCL12 axis in CRC growth, metastasis, angiogenesis, drug resistance, and immune escape. Also, a summary of recent reports concerning targeting CXCR4/CXCL12 axis for CRC management and therapy has been delivered.
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Affiliation(s)
- Ahmed Hjazi
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | | | - Rabia Noor
- Amna Inayat Medical College, Lahore, Pakistan
| | - Ali Alsalamy
- College of Medical Technique, Imam Ja'afar Al-Sadiq University, Al-Muthanna 66002, Iraq
| | - Rahman S Zabibah
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | | | - Muhammad Ikram Ullah
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 75471, Aljouf, Saudi Arabia
| | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul 41001, Iraq
| | - Maytham T Qasim
- Department of Anesthesia, College of Health and Medical Technololgy, Al-Ayen University, Thi-Qar, Iraq
| | - Shaik Vaseem Akram
- Uttaranchal Institute of Technology, Division of Research & Innovation, Uttaranchal University, Dehradun 248007, India
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Sahin TK, Bilir B, Kucuk O. Modulation of inflammation by phytochemicals to enhance efficacy and reduce toxicity of cancer chemotherapy. Crit Rev Food Sci Nutr 2023; 63:2494-2508. [DOI: https:/doi.org/10.1080/10408398.2021.1976721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Affiliation(s)
- Taha Koray Sahin
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Birdal Bilir
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Omer Kucuk
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
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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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12
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Sadeghi M, Dehnavi S, Asadirad A, Xu S, Majeed M, Jamialahmadi T, Johnston TP, Sahebkar A. Curcumin and chemokines: mechanism of action and therapeutic potential in inflammatory diseases. Inflammopharmacology 2023; 31:1069-1093. [PMID: 36997729 DOI: 10.1007/s10787-023-01136-w] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 01/09/2023] [Indexed: 04/01/2023]
Abstract
Chemokines belong to the family of cytokines with chemoattractant properties that regulate chemotaxis and leukocyte migration, as well as the induction of angiogenesis and maintenance of hemostasis. Curcumin, the major component of the Curcuma longa rhizome, has various pharmacological actions, including anti-inflammatory, immune-regulatory, anti-oxidative, and lipid-modifying properties. Chemokines and chemokine receptors are influenced/modulated by curcumin. Thus, the current review focuses on the molecular mechanisms associated with curcumin's effects on chemoattractant cytokines, as well as putting into context the many studies that have reported curcumin-mediated regulatory effects on inflammatory conditions in the organs/systems of the body (e.g., the central nervous system, liver, and cardiovascular system). Curcumin's effects on viral and bacterial infections, cancer, and adverse pregnancy outcomes are also reviewed.
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Affiliation(s)
- Mahvash Sadeghi
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sajad Dehnavi
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Asadirad
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Suowen Xu
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | | | - Tannaz Jamialahmadi
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- School of Medicine, The University of Western Australia, Perth, Australia.
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box, Mashhad, 91779-48564, Iran.
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13
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Lin X, Yang X, Yang Y, Zhang H, Huang X. Research progress of traditional Chinese medicine as sensitizer in reversing chemoresistance of colorectal cancer. Front Oncol 2023; 13:1132141. [PMID: 36994201 PMCID: PMC10040588 DOI: 10.3389/fonc.2023.1132141] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 01/27/2023] [Indexed: 03/14/2023] Open
Abstract
In recent years, the incidences and mortalities from colorectal cancer (CRC) have been increasing; therefore, there is an urgent need to discover newer drugs that enhance drug sensitivity and reverse drug tolerance in CRC treatment. With this view, the current study focuses on understanding the mechanism of CRC chemoresistance to the drug as well as exploring the potential of different traditional Chinese medicine (TCM) in restoring the sensitivity of CRC to chemotherapeutic drugs. Moreover, the mechanism involved in restoring sensitivity, such as by acting on the target of traditional chemical drugs, assisting drug activation, increasing intracellular accumulation of anticancer drugs, improving tumor microenvironment, relieving immunosuppression, and erasing reversible modification like methylation, have been thoroughly discussed. Furthermore, the effect of TCM along with anticancer drugs in reducing toxicity, increasing efficiency, mediating new ways of cell death, and effectively blocking the drug resistance mechanism has been studied. We aimed to explore the potential of TCM as a sensitizer of anti-CRC drugs for the development of a new natural, less-toxic, and highly effective sensitizer to CRC chemoresistance.
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Affiliation(s)
- Xiang Lin
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Xinyu Yang
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Yushang Yang
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Hangbin Zhang
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Xuan Huang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
- *Correspondence: Xuan Huang,
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14
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Alkahtani S, S. AL-Johani N, Alarifi S, Afzal M. Cytotoxicity Mechanisms of Blue-Light-Activated Curcumin in T98G Cell Line: Inducing Apoptosis through ROS-Dependent Downregulation of MMP Pathways. Int J Mol Sci 2023; 24:ijms24043842. [PMID: 36835252 PMCID: PMC9961595 DOI: 10.3390/ijms24043842] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 02/10/2023] [Accepted: 02/11/2023] [Indexed: 02/17/2023] Open
Abstract
We examined the photodynamic activation of Curcumin under blue light in glioblastoma T98G cells. The therapeutic effect of Curcumin, in both the absence and presence of blue light, was measured by the MTT assay and apoptosis progression using flow cytometry. Fluorescence imaging was carried out to evaluate Curcumin uptake. Photodynamic activation of Curcumin (10 µM), in the presence of blue light, enhanced its cytotoxic effect, resulting in the activation of ROS-dependent apoptotic pathways in T98G cells. The gene expression studies showed the expression of matrixes metalloproteinase 2 (MMP2) and 9 (MMP9) decrease with Curcumin (10 µM) under blue light exposure, indicating possible proteolytic mechanisms. Moreover, the cytometric appearance displayed that the expressions of NF-κB and Nrf2 were found to be increased upon exposure to blue light, which revealed a significant induction of expression of nuclear factor as a result of blue-light-induced oxidative stress and cell death. These data further demonstrate that Curcumin exhibited a photodynamic effect via induction of ROS-mediated apoptosis in the presence of blue light. Our results suggest that the application of blue light enhances the therapeutic efficacy of Curcumin in glioblastoma because of the phototherapeutic effect.
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Affiliation(s)
- Saad Alkahtani
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Norah S. AL-Johani
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Saud Alarifi
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Mohd Afzal
- Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
- Correspondence:
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15
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Chen JF, Wu SW, Shi ZM, Hu B. Traditional Chinese medicine for colorectal cancer treatment: potential targets and mechanisms of action. Chin Med 2023; 18:14. [PMID: 36782251 PMCID: PMC9923939 DOI: 10.1186/s13020-023-00719-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 01/30/2023] [Indexed: 02/15/2023] Open
Abstract
Colorectal cancer (CRC) is a disease with complex pathogenesis, it is prone to metastasis, and its development involves abnormalities in multiple signaling pathways. Surgery, chemotherapy, radiotherapy, target therapy, and immunotherapy remain the main treatments for CRC, but improvement in the overall survival rate and quality of life is urgently needed. Traditional Chinese medicine (TCM) has a long history of preventing and treating CRC. It could affect CRC cell proliferation, apoptosis, cell cycle, migration, invasion, autophagy, epithelial-mesenchymal transition, angiogenesis, and chemoresistance by regulating multiple signaling pathways, such as PI3K/Akt, NF-κB, MAPK, Wnt/β-catenin, epidermal growth factor receptors, p53, TGF-β, mTOR, Hedgehog, and immunomodulatory signaling pathways. In this paper, the main signaling pathways and potential targets of TCM and its active ingredients in the treatment of CRC were systematically summarized, providing a theoretical basis for treating CRC with TCM and new ideas for further exploring the pathogenesis of CRC and developing new anti-CRC drugs.
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Affiliation(s)
- Jin-Fang Chen
- grid.412540.60000 0001 2372 7462Institute of Traditional Chinese Medicine in Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032 Shanghai, People’s Republic of China ,grid.412540.60000 0001 2372 7462Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032 Shanghai, People’s Republic of China
| | - Shi-Wei Wu
- grid.412540.60000 0001 2372 7462Institute of Traditional Chinese Medicine in Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032 Shanghai, People’s Republic of China ,grid.412540.60000 0001 2372 7462Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032 Shanghai, People’s Republic of China
| | - Zi-Man Shi
- grid.412540.60000 0001 2372 7462Institute of Traditional Chinese Medicine in Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032 Shanghai, People’s Republic of China ,grid.412540.60000 0001 2372 7462Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032 Shanghai, People’s Republic of China
| | - Bing Hu
- Institute of Traditional Chinese Medicine in Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032, Shanghai, People's Republic of China. .,Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032, Shanghai, People's Republic of China.
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16
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Rao MRP, Ghadge I, Kulkarni S, R. Madgulkar A. Importance of Plant Secondary Metabolites in Modern Therapy. REFERENCE SERIES IN PHYTOCHEMISTRY 2023:1-31. [DOI: 10.1007/978-3-031-30037-0_5-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 07/26/2023] [Indexed: 01/05/2025]
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17
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Koh YC, Tsai YW, Lee PS, Nagabhushanam K, Ho CT, Pan MH. Amination Potentially Augments the Ameliorative Effect of Curcumin on Inhibition of the IL-6/Stat3/c-Myc Pathway and Gut Microbial Modulation in Colitis-Associated Tumorigenesis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:14744-14754. [PMID: 36368792 DOI: 10.1021/acs.jafc.2c06645] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Epigallocatechin gallate and tetrahydrocurcumin are aminated as colonic metabolites, preserving their bioactivities and improving their capabilities. We compared the bioactivities of unaminated (CUR) and aminated (AC) curcumin in inflammatory colitis-associated tumorigenesis. The anti-inflammatory and anticancer capabilities of CUR and AC were evaluated using RAW264.7 and HT29 cell lines, respectively. An azoxymethane/dextran sodium sulfate-induced colitis-associated carcinogenesis mouse model was used with CUR and two-dose AC interventions. AC had a greater anti-inflammatory effect but a similar anticancer effect as CUR in vitro. CUR and low-dose AC (LAC) significantly preserved colon length and reduced tumor number in vivo. Both CUR and LAC inhibited activation of the protein kinase B (AKT)/nuclear factor kappa B (NF-κB) signaling pathway, its downstream cytokines, and the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3)/c-myelocytomatosis oncogene (c-MYC) pathway. However, only LAC significantly preserved E-cadherin, reduced N-cadherin, and facilitated beneficial gut microbial growth, including Akkermansia and Bacteroides, potentially explaining AC's better ameliorative effect at low than high doses.
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Affiliation(s)
- Yen-Chun Koh
- Institute of Food Sciences and Technology, National Taiwan University, Taipei 10617, Taiwan
| | - Yi-Wen Tsai
- Institute of Food Sciences and Technology, National Taiwan University, Taipei 10617, Taiwan
| | - Pei-Sheng Lee
- Institute of Food Sciences and Technology, National Taiwan University, Taipei 10617, Taiwan
| | | | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901, United States
| | - Min-Hsiung Pan
- Institute of Food Sciences and Technology, National Taiwan University, Taipei 10617, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
- Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan
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18
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Layos L, Martínez-Balibrea E, Ruiz de Porras V. Curcumin: A Novel Way to Improve Quality of Life for Colorectal Cancer Patients? Int J Mol Sci 2022; 23:ijms232214058. [PMID: 36430537 PMCID: PMC9695864 DOI: 10.3390/ijms232214058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/07/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women. Treatment of metastatic CRC consists of highly toxic chemotherapeutic drug combinations that often negatively affect patient quality of life (QoL). Moreover, chemotherapy-induced toxicity and chemotherapy resistance are among the most important factors limiting cancer treatment and can lead to the interruption or discontinuation of potentially effective therapy. Several preclinical studies have demonstrated that curcumin acts through multiple cellular pathways and possesses both anti-cancer properties against CRC and the capacity to mitigate chemotherapy-related side effects and overcome drug resistance. In this review article, we suggest that the addition of curcumin to the standard chemotherapeutic treatment for metastatic CRC could reduce associated side-effects and overcome chemotherapy resistance, thereby improving patient QoL.
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Affiliation(s)
- Laura Layos
- Medical Oncology Department, Catalan Institute of Oncology, Ctra. Can Ruti-Camí de les Escoles s/n, 08916 Badalona, Spain
- Catalan Institute of Oncology, Badalona Applied Research Group in Oncology (B·ARGO), Ctra. Can Ruti-Camí de les Escoles s/n, 08916 Badalona, Spain
- Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain
| | - Eva Martínez-Balibrea
- Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain
- ProCURE Program, Catalan Institute of Oncology, Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain
| | - Vicenç Ruiz de Porras
- Catalan Institute of Oncology, Badalona Applied Research Group in Oncology (B·ARGO), Ctra. Can Ruti-Camí de les Escoles s/n, 08916 Badalona, Spain
- Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain
- Correspondence: ; Tel.: +34-(93)-5546301
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19
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Evans AC, Martin KA, Saxena M, Bicher S, Wheeler E, Cordova EJ, Porada CD, Almeida-Porada G, Kato TA, Wilson PF, Coleman MA. Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:nano12203619. [PMID: 36296810 PMCID: PMC9609432 DOI: 10.3390/nano12203619] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 10/01/2022] [Accepted: 10/08/2022] [Indexed: 05/27/2023]
Abstract
Curcumin, a natural polyphenol derived from the spice turmeric (Curcuma longa), contains antioxidant, anti-inflammatory, and anti-cancer properties. However, curcumin bioavailability is inherently low due to poor water solubility and rapid metabolism. Here, we further refined for use curcumin incorporated into "biomimetic" nanolipoprotein particles (cNLPs) consisting of a phospholipid bilayer surrounded by apolipoprotein A1 and amphipathic polymer scaffolding moieties. Our cNLP formulation improves the water solubility of curcumin over 30-fold and produces nanoparticles with ~350 µg/mL total loading capacity for downstream in vitro and in vivo applications. We found that cNLPs were well tolerated in AG05965/MRC-5 human primary lung fibroblasts compared to cultures treated with curcumin solubilized in DMSO (curDMSO). Pre-treatment with cNLPs of quiescent G0/G1-phase MRC-5 cultures improved cell survival following 137Cs gamma ray irradiations, although this finding was reversed in asynchronously cycling log-phase cell cultures. These findings may be useful for establishing cNLPs as a method to improve curcumin bioavailability for administration as a radioprotective and/or radiomitigative agent against ionizing radiation (IR) exposures in non-cycling cells or as a radiosensitizing agent for actively dividing cell populations, such as tumors.
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Affiliation(s)
- Angela C. Evans
- Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
- Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - Kelly A. Martin
- Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - Manoj Saxena
- Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
- Institute of Structural and Molecular Biology, Birkbeck College, University of London, London WC1E 7HX, UK
| | - Sandra Bicher
- Institute of Radiation Medicine, Helmholtz Zentrum München, 85764 Munich, Germany
- Department of Radiation Oncology, Klinikum Rechts der Isar, Technical University Munich (TUM), 81675 Munich, Germany
| | - Elizabeth Wheeler
- Engineering Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
| | - Emilio J. Cordova
- National Institute of Genomic Medicine, Oncogenomic Consortium, Mexico City 14610, Mexico
| | - Christopher D. Porada
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
| | - Graça Almeida-Porada
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
| | - Takamitsu A. Kato
- Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA
| | - Paul F. Wilson
- Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99354, USA
| | - Matthew A. Coleman
- Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
- Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
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20
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Gao Q, Feng J, Liu W, Wen C, Wu Y, Liao Q, Zou L, Sui X, Xie T, Zhang J, Hu Y. Opportunities and challenges for co-delivery nanomedicines based on combination of phytochemicals with chemotherapeutic drugs in cancer treatment. Adv Drug Deliv Rev 2022; 188:114445. [PMID: 35820601 DOI: 10.1016/j.addr.2022.114445] [Citation(s) in RCA: 102] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 06/13/2022] [Accepted: 07/06/2022] [Indexed: 02/08/2023]
Abstract
The therapeutic limitations such as insufficient efficacy, drug resistance, metastasis, and undesirable side effects are frequently caused by the long duration monotherapy based on chemotherapeutic drugs. multiple combinational anticancer strategies such as nucleic acids combined with chemotherapeutic agents, chemotherapeutic combinations, chemotherapy and tumor immunotherapy combinations have been embraced, holding great promise to counter these limitations, while still taking including some potential risks. Nowadays, an increasing number of research has manifested the anticancer effects of phytochemicals mediated by modulating cancer cellular events directly as well as the tumor microenvironment. Specifically, these natural compounds exhibited suppression of cancer cell proliferation, apoptosis, migration and invasion of cancer cells, P-glycoprotein inhibition, decreasing vascularization and activation of tumor immunosuppression. Due to the low toxicity and multiple modulation pathways of these phytochemicals, the combination of chemotherapeutic agents with natural compounds acts as a novel approach to cancer therapy to increase the efficiency of cancer treatments as well as reduce the adverse consequences. In order to achieve the maximized combination advantages of small-molecule chemotherapeutic drugs and natural compounds, a variety of functional nano-scaled drug delivery systems, such as liposomes, host-guest supramolecules, supramolecules, dendrimers, micelles and inorganic systems have been developed for dual/multiple drug co-delivery. These co-delivery nanomedicines can improve pharmacokinetic behavior, tumor accumulation capacity, and achieve tumor site-targeting delivery. In that way, the improved antitumor effects through multiple-target therapy and reduced side effects by decreasing dose can be implemented. Here, we present the synergistic anticancer outcomes and the related mechanisms of the combination of phytochemicals with small-molecule anticancer drugs. We also focus on illustrating the design concept, and action mechanisms of nanosystems with co-delivery of drugs to synergistically improve anticancer efficacy. In addition, the challenges and prospects of how these insights can be translated into clinical benefits are discussed.
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Affiliation(s)
- Quan Gao
- School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Jiao Feng
- School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Wencheng Liu
- School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Chengyong Wen
- School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Yihan Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Qian Liao
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Liang Zou
- Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, No. 2025, Cheng Luo Road, Chengdu 610106, Sichuan, China
| | - Xinbing Sui
- School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
| | - Tian Xie
- School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
| | - Jinming Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Yichen Hu
- Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, No. 2025, Cheng Luo Road, Chengdu 610106, Sichuan, China.
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21
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Liu S, Liu J, He L, Liu L, Cheng B, Zhou F, Cao D, He Y. A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27144400. [PMID: 35889273 PMCID: PMC9319031 DOI: 10.3390/molecules27144400] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/01/2022] [Accepted: 07/05/2022] [Indexed: 12/03/2022]
Abstract
Curcumin is the most important active component in turmeric extracts. Curcumin, a natural monomer from plants has received a considerable attention as a dietary supplement, exhibiting evident activity in a wide range of human pathological conditions. In general, curcumin is beneficial to human health, demonstrating pharmacological activities of anti-inflammation and antioxidation, as well as antitumor and immune regulation activities. Curcumin also presents therapeutic potential in neurodegenerative, cardiovascular and cerebrovascular diseases. In this review article, we summarize the advancements made in recent years with respect to curcumin as a biologically active agent in malignant tumors, Alzheimer’s disease (AD), hematological diseases and viral infectious diseases. We also focus on problems associated with curcumin from basic research to clinical translation, such as its low solubility, leading to poor bioavailability, as well as the controversy surrounding the association between curcumin purity and effect. Through a review and summary of the clinical research on curcumin and case reports of adverse effects, we found that the clinical transformation of curcumin is not successful, and excessive intake of curcumin may have adverse effects on the kidneys, heart, liver, blood and immune system, which leads us to warn that curcumin has a long way to go from basic research to application transformation.
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Affiliation(s)
- Siyu Liu
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
| | - Jie Liu
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
| | - Lan He
- The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410007, China; (L.H.); (B.C.)
| | - Liu Liu
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
| | - Bo Cheng
- The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410007, China; (L.H.); (B.C.)
| | - Fangliang Zhou
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
- Hunan Provincial Engineering and Technological Research Center for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine and Protecting Visual Function, Hunan University of Chinese Medicine, Changsha 410208, China
| | - Deliang Cao
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
- Correspondence: (D.C.); (Y.H.)
| | - Yingchun He
- Post-Graduate School, Hunan University of Chinese Medicine, Changsha 410208, China; (S.L.); (J.L.); (L.L.); (F.Z.)
- Hunan Provincial Engineering and Technological Research Center for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine and Protecting Visual Function, Hunan University of Chinese Medicine, Changsha 410208, China
- Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
- Correspondence: (D.C.); (Y.H.)
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22
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Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells. Cancers (Basel) 2022; 14:cancers14041032. [PMID: 35205780 PMCID: PMC8870219 DOI: 10.3390/cancers14041032] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 02/11/2022] [Accepted: 02/14/2022] [Indexed: 02/06/2023] Open
Abstract
Simple Summary The global burden of colorectal cancer is high. Chemotherapy has been the backbone of colorectal cancer therapy for decades. Toxic side effects and frequently occurring drug resistances remain challenging problems. Therefore, exploring natural compounds with low or even no toxicity holds great potential. However, natural curcumin is poorly absorbed, limiting its clinical use. Therefore, our focus was to screen different molecular types of colorectal cancer to find the ones with the highest sensitivity to curcumin. We observed very individual responses to curcumin for various colorectal cancer cell lines. Most curcumin-sensitive cell lines were of the microsatellite-stable molecular type, and expressed high baseline levels of the IκBα protein. Contrarily, curcumin-resistant lines were mainly microsatellite instable, with low baseline IκBα levels. Considering all of the data obtained, we conclude that patients with microsatellite-stable tumors and high baseline IκBα protein expression would benefit from treatment with novel curcumin formulations and derivatives. Abstract Clinical utilization of curcumin in colorectal cancer (CRC) was revived as a result of the development of novel curcumin formulations with improved bioavailability. Additionally, identification of biomarkers for curcumin sensitivity would also promote successful clinical applications. Here, we wanted to identify such biomarkers in order to establish a predictive model for curcumin sensitivity. Thirty-two low-passage CRC cell lines with specified tumor characteristics were included. Curcumin suppressed cell proliferation, yet sensitivity levels were distinct. Most curcumin-sensitive CRC cell lines were microsatellite stable and expressed high levels of IκBα. The predictive capacity of this biomarker combination possessed a statistical significance of 72% probability to distinguish correctly between curcumin-sensitive and -resistant CRC cell lines. Detailed functional analyses were performed with three sensitive and three resistant CRC cell lines. As curcumin’s mode of action, inhibition of NF-κB p65 activation via IκBα was identified. In consequence, we hypothesize that novel curcumin formulations—either alone or, more likely, in combination with standard therapeutics—can be expected to prove clinically beneficial for CRC patients with high IκBα expression levels.
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Shakeri F, Bibak B, Safdari MR, Keshavarzi Z, Jamialahmadi T, Sathyapalan T, Sahebkar A. Cellular and molecular mechanisms of curcumin on thyroid gland disorders. Curr Med Chem 2022; 29:2878-2890. [PMID: 35142266 DOI: 10.2174/0929867329666220210145033] [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: 05/26/2021] [Revised: 11/13/2021] [Accepted: 11/21/2021] [Indexed: 11/22/2022]
Abstract
There is growing literature on the positive therapeutic potentials of curcumin. Curcumin or diferuloylmethane is a polyphenol obtained from the plant Curcuma longa. Curcumin has been used widely in Ayurvedic and Chinese medicine for various conditions. The role of curcumin on thyroid glands has been shown by its effects on various biological pathways, including anti-inflammatory, antioxidant, anti-proliferative, apoptosis, angiogenesis, cell cycle and metastasis. We reviewed the recent literature on curcumin applications for thyroid dysfunction, including hyperthyroidism and hypothyroidism, and discussed the molecular mechanisms of these effects. This review aims to summarize the wealth of research related to the thyroid gland therapeutic effect of curcumin.
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Affiliation(s)
- Farzaneh Shakeri
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Bahram Bibak
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mohammad Reza Safdari
- Department of Orthopedic Surgery, Imam Ali Hospital, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Zakieh Keshavarzi
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Tannaz Jamialahmadi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Thozhukat Sathyapalan
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Verma E, Kumar A, Devi Daimary U, Parama D, Girisa S, Sethi G, Kunnumakkara AB. Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104660] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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Kunnumakkara AB, Rana V, Parama D, Banik K, Girisa S, Henamayee S, Thakur KK, Dutta U, Garodia P, Gupta SC, Aggarwal BB. COVID-19, cytokines, inflammation, and spices: How are they related? Life Sci 2021; 284:119201. [PMID: 33607159 PMCID: PMC7884924 DOI: 10.1016/j.lfs.2021.119201] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/20/2021] [Accepted: 01/30/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-19 associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/) in the USA is high (1199/million) as compared to countries like India (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties. AIM To evaluate the literature available on the anti-inflammatory properties of spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm. METHOD A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19, and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm. KEY FINDINGS The literature search resulted in numerous in vitro, in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation. SIGNIFICANCE As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm.
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Affiliation(s)
- Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India.
| | - Varsha Rana
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Dey Parama
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Kishore Banik
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Sosmitha Girisa
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Sahu Henamayee
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Krishan Kumar Thakur
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Uma Dutta
- Cell and Molecular Biology Lab, Department of Zoology, Cotton University, Guwahati, Assam 781001, India
| | | | - Subash C Gupta
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India
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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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Sahin TK, Bilir B, Kucuk O. Modulation of inflammation by phytochemicals to enhance efficacy and reduce toxicity of cancer chemotherapy. Crit Rev Food Sci Nutr 2021; 63:2494-2508. [PMID: 34529530 DOI: 10.1080/10408398.2021.1976721] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Treatment of cancer with chemotherapeutic drugs is associated with numerous adverse effects as well as the eventual development of resistance to chemotherapy. There is a great need for complementary therapies such as botanicals and nutritional supplements with little or no side effects that prevent resistance to chemotherapy and reduce its adverse effects. Inflammation plays a major role in the development of chemoresistance and the adverse effects of chemotherapy. Phytochemicals have well-established anti-inflammatory effects; thus, they could be used as complementary therapies along with chemotherapy to increase its efficacy and reduce its toxicity. Botanical compounds inhibit the NF-κB signaling pathway, which plays an important role in the generation of inflammation, chemotherapy resistance, and modulation of cell survival and apoptosis. Botanicals have previously been studied extensively for their cancer chemopreventive activities and are generally considered safe for human consumption. The present review focuses on the modulation of inflammation by phytochemicals and their role in increasing the efficacy and reducing the toxicity of cancer chemotherapy.
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Affiliation(s)
- Taha Koray Sahin
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Birdal Bilir
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Omer Kucuk
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
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28
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Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance. Cancers (Basel) 2021; 13:cancers13174363. [PMID: 34503172 PMCID: PMC8430856 DOI: 10.3390/cancers13174363] [Citation(s) in RCA: 178] [Impact Index Per Article: 44.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/21/2021] [Accepted: 08/26/2021] [Indexed: 12/25/2022] Open
Abstract
Simple Summary Despite recent therapeutic advances against cancer, many patients do not respond well or respond poorly, to treatment and develop resistance to more than one anti-cancer drug, a term called multi-drug resistance (MDR). One of the main factors that contribute to MDR is the deregulation of apoptosis or programmed cell death. Herein, we describe the major apoptotic pathways and discuss how pro-apoptotic and anti-apoptotic proteins are modified in cancer cells to convey drug resistance. We also focus on our current understanding related to the interactions between survival and cell death pathways, as well as on mechanisms underlying the balance shift towards cancer cell growth and drug resistance. Moreover, we highlight the role of the tumor microenvironment components in blocking apoptosis in MDR tumors, and we discuss the significance and potential exploitation of epigenetic modifications for cancer treatment. Finally, we summarize the current and future therapeutic approaches for overcoming MDR. Abstract The ability of tumor cells to evade apoptosis is established as one of the hallmarks of cancer. The deregulation of apoptotic pathways conveys a survival advantage enabling cancer cells to develop multi-drug resistance (MDR), a complex tumor phenotype referring to concurrent resistance toward agents with different function and/or structure. Proteins implicated in the intrinsic pathway of apoptosis, including the Bcl-2 superfamily and Inhibitors of Apoptosis (IAP) family members, as well as their regulator, tumor suppressor p53, have been implicated in the development of MDR in many cancer types. The PI3K/AKT pathway is pivotal in promoting survival and proliferation and is often overactive in MDR tumors. In addition, the tumor microenvironment, particularly factors secreted by cancer-associated fibroblasts, can inhibit apoptosis in cancer cells and reduce the effectiveness of different anti-cancer drugs. In this review, we describe the main alterations that occur in apoptosis-and related pathways to promote MDR. We also summarize the main therapeutic approaches against resistant tumors, including agents targeting Bcl-2 family members, small molecule inhibitors against IAPs or AKT and agents of natural origin that may be used as monotherapy or in combination with conventional therapeutics. Finally, we highlight the potential of therapeutic exploitation of epigenetic modifications to reverse the MDR phenotype.
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Davoodvandi A, Farshadi M, Zare N, Akhlagh SA, Alipour Nosrani E, Mahjoubin-Tehran M, Kangari P, Sharafi SM, Khan H, Aschner M, Baniebrahimi G, Mirzaei H. Antimetastatic Effects of Curcumin in Oral and Gastrointestinal Cancers. Front Pharmacol 2021; 12:668567. [PMID: 34456716 PMCID: PMC8386020 DOI: 10.3389/fphar.2021.668567] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 07/05/2021] [Indexed: 12/17/2022] Open
Abstract
Gastrointestinal (GI) cancers are known as frequently occurred solid malignant tumors that can cause the high rate mortality in the world. Metastasis is a significant destructive feature of tumoral cells, which directly correlates with decreased prognosis and survival. Curcumin, which is found in turmeric, has been identified as a potent therapeutic natural bioactive compound (Curcuma longa). It has been traditionally applied for centuries to treat different diseases, and it has shown efficacy for its anticancer properties. Numerous studies have revealed that curcumin inhibits migration and metastasis of GI cancer cells by modulating various genes and proteins, i.e., growth factors, inflammatory cytokines and their receptors, different types of enzymes, caspases, cell adhesion molecules, and cell cycle proteins. Herein, we summarized the antimetastatic effects of curcumin in GI cancers, including pancreatic cancer, gastric cancer, colorectal cancer, oral cancer, and esophageal cancer.
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Affiliation(s)
- Amirhossein Davoodvandi
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | | | - Noushid Zare
- Faculty of Pharmacy, International Campus, Tehran University of Medical Science, Tehran, Iran
| | | | - Esmail Alipour Nosrani
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Maryam Mahjoubin-Tehran
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Parisa Kangari
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyedeh Maryam Sharafi
- Environment Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Ghazaleh Baniebrahimi
- Department of Pediatric Dentistry, School of Dentistry, Tehran University of Medical Sciences, Tehran, 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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Morshedi K, Borran S, Ebrahimi MS, Masoud Khooy MJ, Seyedi ZS, Amiri A, Abbasi-Kolli M, Fallah M, Khan H, Sahebkar A, Mirzaei H. Therapeutic effect of curcumin in gastrointestinal cancers: A comprehensive review. Phytother Res 2021; 35:4834-4897. [PMID: 34173992 DOI: 10.1002/ptr.7119] [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: 11/30/2020] [Revised: 02/18/2021] [Accepted: 03/26/2021] [Indexed: 12/11/2022]
Abstract
Gastrointestinal (GI) cancers with a high global prevalence are a leading cause of morbidity and mortality. Accordingly, there is a great need to develop efficient therapeutic approaches. Curcumin, a naturally occurring agent, is a promising compound with documented safety and anticancer activities. Recent studies have demonstrated the activity of curcumin in the prevention and treatment of different cancers. According to systematic studies on curcumin use in various diseases, it can be particularly effective in GI cancers because of its high bioavailability in the gastrointestinal tract. Nevertheless, the clinical applications of curcumin are largely limited because of its low solubility and low chemical stability in water. These limitations may be addressed by the use of relevant analogues or novel delivery systems. Herein, we summarize the pharmacological effects of curcumin against GI cancers. Moreover, we highlight the application of curcumin's analogues and novel delivery systems in the treatment of GI cancers.
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Affiliation(s)
- Korosh Morshedi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Sarina Borran
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | | | - Zeynab Sadat Seyedi
- Department of Cell and Molecular Biology, Faculty of Chemistry, University of Kashan, Kashan, Iran
| | - Atefeh Amiri
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Abbasi-Kolli
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Maryam Fallah
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, 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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El-Far AH, Elewa YHA, Abdelfattah EZA, Alsenosy AWA, Atta MS, Abou-Zeid KM, Al Jaouni SK, Mousa SA, Noreldin AE. RETRACTED: Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats' Brain and Heart. Int J Mol Sci 2021; 22:6839. [PMID: 34202112 PMCID: PMC8268720 DOI: 10.3390/ijms22136839] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 06/09/2021] [Accepted: 06/18/2021] [Indexed: 01/17/2023] Open
Abstract
D-galactose (D-gal) administration causes oxidative disorder and is widely utilized in aging animal models. Therefore, we subcutaneously injected D-gal at 200 mg/kg BW dose to assess the potential preventive effect of thymoquinone (TQ) and curcumin (Cur) against the oxidative alterations induced by D-gal. Other than the control, vehicle, and D-gal groups, the TQ and Cur treated groups were orally supplemented at 20 mg/kg BW of each alone or combined. TQ and Cur effectively suppressed the oxidative alterations induced by D-gal in brain and heart tissues. The TQ and Cur combination significantly decreased the elevated necrosis in the brain and heart by D-gal. It significantly reduced brain caspase 3, calbindin, and calcium-binding adapter molecule 1 (IBA1), heart caspase 3, and BCL2. Expression of mRNA of the brain and heart TP53, p21, Bax, and CASP-3 were significantly downregulated in the TQ and Cur combination group along with upregulation of BCL2 in comparison with the D-gal group. Data suggested that the TQ and Cur combination is a promising approach in aging prevention.
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Affiliation(s)
- Ali H. El-Far
- Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt;
| | - Yaser H. A. Elewa
- Department of Histology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt
- Laboratory of Anatomy, Faculty of Veterinary Medicine, Basic Veterinary Sciences, Hokkaido University, Sapporo 060-0818, Japan
| | | | - Abdel-Wahab A. Alsenosy
- Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt;
| | - Mustafa S. Atta
- Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt;
| | - Khalid M. Abou-Zeid
- Animal Care Unit, Medical Research Institute, Alexandria University, Alexandria 21544, Egypt; (E.-Z.A.A.); (K.M.A.-Z.)
| | - Soad K. Al Jaouni
- Department of Hematology/Pediatric Oncology, Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Shaker A. Mousa
- Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA;
| | - Ahmed E. Noreldin
- Histology and Cytology Department, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt;
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Yammine A, Namsi A, Vervandier-Fasseur D, Mackrill JJ, Lizard G, Latruffe N. Polyphenols of the Mediterranean Diet and Their Metabolites in the Prevention of Colorectal Cancer. Molecules 2021; 26:3483. [PMID: 34201125 PMCID: PMC8227701 DOI: 10.3390/molecules26123483] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/03/2021] [Accepted: 06/04/2021] [Indexed: 02/07/2023] Open
Abstract
The Mediterranean diet is a central element of a healthy lifestyle, where polyphenols play a key role due to their anti-oxidant properties, and for some of them, as nutripharmacological compounds capable of preventing a number of diseases, including cancer. Due to the high prevalence of intestinal cancer (ranking second in causing morbidity and mortality), this review is focused on the beneficial effects of selected dietary phytophenols, largely present in Mediterranean cooking: apigenin, curcumin, epigallocatechin gallate, quercetin-rutine, and resveratrol. The role of the Mediterranean diet in the prevention of colorectal cancer and future perspectives are discussed in terms of food polyphenol content, the effectiveness, the plasma level, and the importance of other factors, such as the polyphenol metabolites and the influence of the microbiome. Perspectives are discussed in terms of microbiome-dependency of the brain-second brain axis. The emergence of polyphenol formulations may strengthen the efficiency of the Mediterranean diet in the prevention of cancer.
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Affiliation(s)
- Aline Yammine
- Team Bio-PeroxIL, “Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism” (EA7270), University of Bourgogne Franche-Comté, Inserm, 21000 Dijon, France; (A.Y.); (A.N.); (G.L.)
| | - Amira Namsi
- Team Bio-PeroxIL, “Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism” (EA7270), University of Bourgogne Franche-Comté, Inserm, 21000 Dijon, France; (A.Y.); (A.N.); (G.L.)
| | - Dominique Vervandier-Fasseur
- Team OCS, Institute of Molecular Chemistry of University of Burgundy (ICMUB UMR CNRS 6302), University of Bourgogne Franche-Comté, 21000 Dijon, France;
| | - John J. Mackrill
- Department of Physiology, University College Cork, BioScience Institute, College Road, T12 YT20 Cork, Ireland;
| | - Gérard Lizard
- Team Bio-PeroxIL, “Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism” (EA7270), University of Bourgogne Franche-Comté, Inserm, 21000 Dijon, France; (A.Y.); (A.N.); (G.L.)
| | - Norbert Latruffe
- Team Bio-PeroxIL, “Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism” (EA7270), University of Bourgogne Franche-Comté, Inserm, 21000 Dijon, France; (A.Y.); (A.N.); (G.L.)
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Pouya FD, Rasmi Y, Camci IY, Tutar Y, Nemati M. Performance of capecitabine in novel combination therapies in colorectal cancer. J Chemother 2021; 33:375-389. [PMID: 34019782 DOI: 10.1080/1120009x.2021.1920247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Colorectal cancer is one of the most common cancers throughout the world, and no definitive cure has ever been found. Perhaps a new insight into the effectiveness of chemotherapy drugs could help better treat patients. Targeted therapies have significantly improved the median overall survival of colorectal cancer patients. One of the standard chemotherapy regimens used for colorectal cancer is capecitabine, which is important in monotherapy and combination therapies. Capecitabine, with other chemotherapeutic agents (irinotecan, oxaliplatin, perifosine, 17-allylamino-17-demethoxygeldanamycin, aspirin, celecoxib, statins, quinacrine, inositol hexaphosphate and inositol, cystine/theanine, curcumin, and isorhamnetin), and biological ones (antibodies) plays an important role in the inhibition of some signaling pathways, increasing survival, reducing tumor growth and side effects of capecitabine. However, some drugs, such as proton pump inhibitors, are negatively related to capecitabine; therefore, the purpose of this work is to review and discuss the performance of capecitabine combination therapies in colorectal cancer.
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Affiliation(s)
- Fahima Danesh Pouya
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Yousef Rasmi
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.,Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
| | - Irem Yalim Camci
- Department of Molecular Biology and Genetics, Faculty of Science, Gebze Technical University, Kocaeli, Turkey
| | - Yusuf Tutar
- Division of Biochemistry, Department of Basic Pharmaceutical Sciences, Hamidiye Faculty of Pharmacy, University of Health Sciences, Turkey Istanbul
| | - Mohadeseh Nemati
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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Girisa S, Kumar A, Rana V, Parama D, Daimary UD, Warnakulasuriya S, Kumar AP, Kunnumakkara AB. From Simple Mouth Cavities to Complex Oral Mucosal Disorders-Curcuminoids as a Promising Therapeutic Approach. ACS Pharmacol Transl Sci 2021; 4:647-665. [PMID: 33860191 PMCID: PMC8033761 DOI: 10.1021/acsptsci.1c00017] [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: 01/09/2021] [Indexed: 02/08/2023]
Abstract
Oral diseases are among the most common encountered health issues worldwide, which are usually associated with anomalies of the oral cavity, jaws, and salivary glands. Despite the availability of numerous treatment modalities for oral disorders, a limited clinical response has been observed because of the inefficacy of the drugs and countless adverse side effects. Therefore, the development of safe, efficacious, and wide-spectrum therapeutics is imperative in the battle against oral diseases. Curcumin, extracted from the golden spice turmeric, is a well-known natural polyphenol that has been extensively studied for its broad pleiotropic attributes and its ability to modulate multiple biological processes. It is well-documented to target pro-inflammatory mediators like NF-κB, ROS, COX-2, IL-1, IL-2, TGF-β, growth factors, apoptotic proteins, receptors, and various kinases. These properties make curcumin a promising nutraceutical in the treatment of many oral diseases like oral submucous fibrosis, oral mucositis, oral leukoplakia, oral erythroplakia, oral candidiasis, aphthous stomatitis, oral lichen planus, dental caries, periodontitis, and gingivitis. Numerous in vitro and in vivo studies have shown that curcumin alleviates the symptoms of most of the oral complications, including the inhibition of the progression of oral cancer. In this regard, many clinical trials have been completed, and many are ongoing to investigate the "curcumin effect" in oral maladies. Therefore, the current review delineates the mechanistic framework of curcumin's propensity in curbing oral diseases and present outcomes of the clinical trials of curcumin-based therapeutics that can provide a breakthrough in the clinical management of these diseases.
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Affiliation(s)
- Sosmitha Girisa
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
| | - Aviral Kumar
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
| | - Varsha Rana
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
| | - Dey Parama
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
| | - Uzini Devi Daimary
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
| | - Saman Warnakulasuriya
- Department
of Oral Medicine, King’s College
London and WHO Collaborating Centre for Oral Cancer and Precancer, London WC2R 2LS, United Kingdom
| | - Alan Prem Kumar
- Medical
Science Cluster, Cancer Translational Research Programme, Yong Loo
Lin School of Medicine, National University
of Singapore, Singapore 117600, Singapore
- Cancer
Science Institute of Singapore, National
University of Singapore, Singapore 117600, Singapore
- National
University Cancer Institute, National University
Health Systems, Singapore 117600, Singapore
| | - Ajaikumar B. Kunnumakkara
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
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Bhatia M, Bhalerao M, Cruz-Martins N, Kumar D. Curcumin and cancer biology: Focusing regulatory effects in different signalling pathways. Phytother Res 2021; 35:4913-4929. [PMID: 33837579 DOI: 10.1002/ptr.7121] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 03/20/2021] [Accepted: 03/26/2021] [Indexed: 12/20/2022]
Abstract
Cancer is the second-leading cause of death worldwide. Till date, many such effective treatments are available, for example chemotherapy, surgery, and radiation therapy, but there are severe associated side effects, such as increased infection risk, constipation, hair loss, anaemia, among others. Thus, the need for effective therapeutic strategies and screening methodology arises. Researchers around the world are increasingly trying to discover anticancer therapies with as few side effects as possible and many are now focusing on phytochemicals, like curcumin. Curcumin is a bright yellow substance isolated from the plant rhizomes of Curcuma longa L. To this molecule a high therapeutic benefit has been underlined, being able to alter the development of cancer by different mechanisms, such as regulating multiple microRNA expression, modifying a series of signalling pathways, that is, Akt, Bcl-2, PTEN, p53, Notch, and Erbb. Another major pathway that curcumin targets is the matrix metalloproteinase (MMP) gene expression. In fact, MMPs are responsible for the degradation of the cell-extracellular matrix, which can lead to the diseased condition and many different pathways contribute to its activity, such as JAK/STAT, NF-κB, MAPK/ERK, COX-2, ROS, TGF-β, among others. In this review, we have attempted to describe the curcumin regulatory effect on different cell signalling pathways involved in the progression of different types of cancers.
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Affiliation(s)
- Muskan Bhatia
- Poona college of pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Mihir Bhalerao
- Poona college of pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Natália Cruz-Martins
- Faculty of Medicine, University of Porto, Porto, Portugal.,Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal.,Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | - Dileep Kumar
- Poona college of pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, India
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Harikrishnan A, Khanna S, Veena V. Design of New Improved Curcumin Derivatives to Multi-targets of Cancer and Inflammation. Curr Drug Targets 2021; 22:573-589. [PMID: 32753008 DOI: 10.2174/1389450121666200804113745] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/11/2020] [Accepted: 05/11/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Curcumin is a major active principle of Curcuma longa. There are more than 1700 citations in the Medline, reflecting various biological effects of curcumin. Most of these biological activities are associated with the antioxidant, anti-inflammatory and antitumor activity of the molecule. Several reports suggest various targets of natural curcumin that include growth factors, growth factor receptor, cytokines, enzymes and gene regulators of apoptosis. This review focuses on the improved curcumin derivatives that target the cancer and inflammation. METHODOLOGY In this present review, we explored the anticancer drugs with curcumin-based drugs under pre-clinical and clinical studies with critical examination. Based on the strong scientific reports of patentable and non-patented literature survey, we have investigated the mode of the interactions of curcumin-based molecules with the target molecules. RESULTS Advanced studies have added new dimensions of the molecular response of cancer cells to curcumin at the genomic level. However, poor bioavailability of the molecule seems to be the major limitation of the curcumin. Several researchers have been involved to improve the curcumin derivatives to overcome this limitation. Sufficient data of clinical trials to various cancers that include multiple myeloma, pancreatic cancer and colon cancer, have also been discussed. CONCLUSION The detailed analysis of the structure-activity relationship (SAR) and common synthesis of curcumin-based derivatives have been discussed in the review. Utilising the predictions of in silico coupled with validation reports of in vitro and in vivo studies have concluded many targets for curcumin. Among them, cancer-related inflammation genes regulating curcumin-based molecules are a very promising target to overcome hurdles in the multimodality therapy of cancer.
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Affiliation(s)
- A Harikrishnan
- Department of Chemistry, School of Arts and Sciences, Vinayaka Mission Research Foundation-Aarupadai Veedu (VMRF-AV) campus, Paiyanoor, Chennai-603104, Tamil Nadu, India
| | - Sunali Khanna
- Nair Hospital Dental College, Municipal Corporation of Greater Mumbai, Mumbai, 400 008, India
| | - V Veena
- Department of Biotechnology, School of Applied Sciences, REVA University, Rukmini knowledge park, Kattigenahalli, Yelahanka, Bengaluru - 5600 064. Karnataka State, India
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Potential Role of Curcumin and Its Nanoformulations to Treat Various Types of Cancers. Biomolecules 2021; 11:biom11030392. [PMID: 33800000 PMCID: PMC8001478 DOI: 10.3390/biom11030392] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/27/2021] [Accepted: 03/03/2021] [Indexed: 12/17/2022] Open
Abstract
Cancer is a major burden of disease globally. Each year, tens of millions of people are diagnosed with cancer worldwide, and more than half of the patients eventually die from it. Significant advances have been noticed in cancer treatment, but the mortality and incidence rates of cancers are still high. Thus, there is a growing research interest in developing more effective and less toxic cancer treatment approaches. Curcumin (CUR), the major active component of turmeric (Curcuma longa L.), has gained great research interest as an antioxidant, anticancer, and anti-inflammatory agent. This natural compound shows its anticancer effect through several pathways including interfering with multiple cellular mechanisms and inhibiting/inducing the generation of multiple cytokines, enzymes, or growth factors including IκB kinase β (IκKβ), tumor necrosis factor-alpha (TNF-α), signal transducer, and activator of transcription 3 (STAT3), cyclooxygenase II (COX-2), protein kinase D1 (PKD1), nuclear factor-kappa B (NF-κB), epidermal growth factor, and mitogen-activated protein kinase (MAPK). Interestingly, the anticancer activity of CUR has been limited primarily due to its poor water solubility, which can lead to low chemical stability, low oral bioavailability, and low cellular uptake. Delivering drugs at a controlled rate, slow delivery, and targeted delivery are other very attractive methods and have been pursued vigorously. Multiple CUR nanoformulations have also been developed so far to ameliorate solubility and bioavailability of CUR and to provide protection to CUR against hydrolysis inactivation. In this review, we have summarized the anticancer activity of CUR against several cancers, for example, gastrointestinal, head and neck, brain, pancreatic, colorectal, breast, and prostate cancers. In addition, we have also focused on the findings obtained from multiple experimental and clinical studies regarding the anticancer effect of CUR in animal models, human subjects, and cancer cell lines.
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Chuang HY, Tyan YS, Hwang JJ, Shih KC, Lin WC. A combination of sorafenib and radiotherapy reduces NF-κB activity and growth of hepatocellular carcinoma in an orthotopic mouse model. Oncol Lett 2021; 21:337. [PMID: 33692869 PMCID: PMC7933744 DOI: 10.3892/ol.2021.12598] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 01/18/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is difficult to diagnose at an early stage, and its prognosis is generally poor. Sorafenib is the primary treatment for unresectable advanced HCC and targets multiple receptor tyrosine kinases. However, sorafenib only extends the average survival time by 3 months. This observation indicates that sorafenib may need to be combined with other treatments to further improve outcomes. We previously showed that combination of sorafenib with radiotherapy (RT) enhances tumor inhibition in subcutaneous HCC mouse models compared with monotherapy. The present study demonstrated that combining sorafenib and RT could suppress tumor growth in an orthotopic HCC model by regulating apoptosis and NF-κB-related pathways. Moreover, decreased numbers of visible liver tumors and a smaller percentage of spleen metastases were found in the combination group. A transient drop in body weight was initially observed after RT, but progressive recovery of body weight occurred. The current study showed that the combination of sorafenib and RT could be a safe strategy for HCC treatment.
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Affiliation(s)
- Hui-Yen Chuang
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan, R.O.C
| | - Yeu-Sheng Tyan
- Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung 402, Taiwan, R.O.C
| | - Jeng-Jong Hwang
- Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung 402, Taiwan, R.O.C.,Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C
| | - Kuang-Chung Shih
- Division of Endocrinology and Metabolism, Department of Medicine, Cheng-Hsin General Hospital, Taipei 112, Taiwan, R.O.C.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, R.O.C
| | - Wei-Chan Lin
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan, R.O.C.,Department of Radiology, Cathay General Hospital, New Taipei 106, Taiwan, R.O.C.,School of Medicine, Fu-Jen Catholic University, New Taipei 106, Taiwan, R.O.C
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Chung SY, Chao TC, Su Y. The Stemness-High Human Colorectal Cancer Cells Promote Angiogenesis by Producing Higher Amounts of Angiogenic Cytokines via Activation of the Egfr/Akt/Nf-κB Pathway. Int J Mol Sci 2021; 22:ijms22031355. [PMID: 33573006 PMCID: PMC7866396 DOI: 10.3390/ijms22031355] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 01/22/2021] [Accepted: 01/27/2021] [Indexed: 12/27/2022] Open
Abstract
Purpose: Cancer stem cells (CSCs) are responsible for cancer metastasis by stimulating tumor angiogenesis via various mechanisms. To elucidate the potential of the stemness-high human colorectal cancer (CRC) cells (i.e., CRCSCs) in activating angiogenesis, effects of the GATA6-overexpressing HCT-116 and HT-29 human CRC clones established previously by us in promoting the angiogenesis of human umbilical vein endothelial cells (HUVECs) were examined. Methods: Angiogenesis-promoting effects (i.e., migration, invasion, DNA synthesis, and tube formation) in HUVECs of the conditioned media (CM) from various human CRC clones were analyzed. MMP activities were assessed using a zymography assay. Western blotting and selective inhibitors were used to dissect the signaling pathway involved. IHC was used to examine the vascular density in tumor xenografts. Results: We found that the conditioned media (CM) collected from the GATA6-overexpressing clones enhanced angiogenesis of HUVECs more effectively which might be attributed partly to a higher MMP-9 production by HUVECs. Subsequently, elevated levels of IL-8 and VEGF-A were detected in the CM whose tube formation-enhancing activities were abolished by the co-treatment with either a VEGFR2 inhibitor or an IL-8 neutralizing antibody. Interestingly, increased production of these cytokines in the GATA6-overexpressing clones was due to an EGFR/AKT-mediated activation of NF-κB. Furthermore, not only were the levels of CD31 and endomucin but also the blood vessel density was much higher in the xenograft tumors grown from these clones. Conclusion: Our findings demonstrate that human CRCSCs promote a stronger angiogenesis by producing higher amounts of angiogenic factors through activation of the EGFR/AKT/NF-κB pathway.
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Affiliation(s)
- Shin-Yi Chung
- Institute of Biopharmaceutical Sciences, School of Pharmaceutical Sciences, National Yang-Ming University, Shi-Pai, Taipei 11221, Taiwan;
| | - Ta-Chung Chao
- Department of Oncology, Division of Medical Oncology, Taipei Veterans General Hospital, Taipei 11221, Taiwan;
- Faculty of Medicine, School of Medicine, National Yang-Min University, Taipei 11221, Taiwan
| | - Yeu Su
- Institute of Biopharmaceutical Sciences, School of Pharmaceutical Sciences, National Yang-Ming University, Shi-Pai, Taipei 11221, Taiwan;
- Correspondence: ; Fax: +886-2-2825-0883
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Ahmed SA, Parama D, Daimari E, Girisa S, Banik K, Harsha C, Dutta U, Kunnumakkara AB. Rationalizing the therapeutic potential of apigenin against cancer. Life Sci 2020; 267:118814. [PMID: 33333052 DOI: 10.1016/j.lfs.2020.118814] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 11/14/2020] [Accepted: 11/20/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Despite the remarkable advances made in the diagnosis and treatment of cancer during the past couple of decades, it remains the second largest cause of mortality in the world, killing approximately 9.6 million people annually. The major challenges in the treatment of the advanced stage of this disease are the development of chemoresistance, severe adverse effects of the drugs, and high treatment cost. Therefore, the development of drugs that are safe, efficacious, and cost-effective remains a 'Holy Grail' in cancer research. However, the research over the past four decades shed light on the cancer-preventive and therapeutic potential of natural products and their underlying mechanism of action. Apigenin is one such compound, which is known to be safe and has significant potential in the prevention and therapy of this disease. AIM To assess the literature available on the potential of apigenin and its analogs in modulating the key molecular targets leading to the prevention and treatment of different types of cancer. METHOD A comprehensive literature search has been carried out on PubMed for obtaining information related to the sources and analogs, chemistry and biosynthesis, physicochemical properties, biological activities, bioavailability and toxicity of apigenin. KEY FINDINGS The literature search resulted in many in vitro, in vivo and a few cohort studies that evidenced the effectiveness of apigenin and its analogs in modulating important molecular targets and signaling pathways such as PI3K/AKT/mTOR, JAK/STAT, NF-κB, MAPK/ERK, Wnt/β-catenin, etc., which play a crucial role in the development and progression of cancer. In addition, apigenin was also shown to inhibit chemoresistance and radioresistance and make cancer cells sensitive to these agents. Reports have further revealed the safety of the compound and the adaptation of nanotechnological approaches for improving its bioavailability. SIGNIFICANCE Hence, the present review recapitulates the properties of apigenin and its pharmacological activities against different types of cancer, which warrant further investigation in clinical settings.
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Affiliation(s)
- Semim Akhtar Ahmed
- Cell and Molecular Biology Laboratory, Department of Zoology, Cotton University, Pan Bazar, Guwahati, Assam 781001, India
| | - Dey Parama
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India
| | - Enush Daimari
- Cell and Molecular Biology Laboratory, Department of Zoology, Cotton University, Pan Bazar, Guwahati, Assam 781001, India
| | - Sosmitha Girisa
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India
| | - Kishore Banik
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India
| | - Choudhary Harsha
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India
| | - Uma Dutta
- Cell and Molecular Biology Laboratory, Department of Zoology, Cotton University, Pan Bazar, Guwahati, Assam 781001, India.
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India.
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Martinovich GG, Martinovich IV, Vcherashniaya AV, Zenkov NK, Menshchikova EB, Cherenkevich SN. Chemosensitization of Tumor Cells by Phenolic Antioxidants: The Role of the Nrf2 Transcription Factor. Biophysics (Nagoya-shi) 2020. [DOI: 10.1134/s000635092006010x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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Girisa S, Parama D, Harsha C, Banik K, Kunnumakkara AB. Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2020; 1:313-342. [PMID: 36046484 PMCID: PMC9400725 DOI: 10.37349/etat.2020.00019] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 09/14/2020] [Indexed: 12/13/2022] Open
Abstract
Cancer is one of the most dreadful diseases in the world with a mortality of 9.6 million annually. Despite the advances in diagnosis and treatment during the last couple of decades, it still remains a serious concern due to the limitations associated with currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. The importance of medicinal plants as primary healthcare has been well-known from time immemorial against various human diseases, including cancer. Commiphora wightii that belongs to Burseraceae family is one such plant which has been used to cure various ailments in traditional systems of medicine. This plant has diverse pharmacological properties such as antioxidant, antibacterial, antimutagenic, and antitumor which mostly owes to the presence of its active compound guggulsterone (GS) that exists in the form of Z- and E-isomers. Mounting evidence suggests that this compound has promising anticancer activities and was shown to suppress several cancer signaling pathways such as NF-κB/ERK/MAPK/AKT/STAT and modulate the expression of numerous signaling molecules such as the farnesoid X receptor, cyclin D1, survivin, caspases, HIF-1α, MMP-9, EMT proteins, tumor suppressor proteins, angiogenic proteins, and apoptotic proteins. The current review is an attempt to summarize the biological activities and diverse anticancer activities (both in vitro and in vivo) of the compound GS and its derivatives, along with its associated mechanism against various cancers.
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Affiliation(s)
- Sosmitha Girisa
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Dey Parama
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Choudhary Harsha
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Kishore Banik
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
| | - Ajaikumar B. Kunnumakkara
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India
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Zhai K, Brockmüller A, Kubatka P, Shakibaei M, Büsselberg D. Curcumin's Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions. Biomolecules 2020; 10:biom10111469. [PMID: 33105719 PMCID: PMC7690450 DOI: 10.3390/biom10111469] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 10/17/2020] [Accepted: 10/19/2020] [Indexed: 02/07/2023] Open
Abstract
Curcumin, a natural polyphenolic compound derived from the South Asian turmeric plant (Curcuma longa), has well-characterized antioxidant, anti-inflammatory, anti-protein-aggregate, and anticancer properties. Neuroblastoma (NB) is a cancer of the nervous system that arises primarily in pediatric patients. In order to reduce the multiple disadvantages and side effects of conventional oncologic modalities and to potentially overcome cancer drug resistance, natural substances such as curcumin are examined as complementary and supportive therapies against NB. In NB cell lines, curcumin by itself promotes apoptosis and cell cycle arrest through the suppression of serine–threonine kinase Akt and nuclear factor kappa of activated B-cells (NF-κB) signaling, induction of mitochondrial dysfunction, and upregulation of p53 and caspase signaling. While curcumin demonstrates anti-NB efficacy in vitro, cross-validation between NB cell types is currently lacking for many of its specific mechanistic activities. Furthermore, curcumin’s low bioavailability by oral administration, poor absorption, and relative insolubility in water pose challenges to its clinical introduction. Numerous curcumin formulations, including nanoparticles, nanocarriers, and microemulsions, have been developed, with these having some success in the treatment of NB. In the future, standardization and further basic and preclinical trials will be required to ensure the safety of curcumin formulations. While the administration of curcumin is clinically safe even at high doses, clinical trials are necessary to substantiate the practical efficacy of curcumin in the prevention and treatment of NB.
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Affiliation(s)
- Kevin Zhai
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar;
| | - Aranka Brockmüller
- Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilian-University Munich, 80336 Munich, Germany; (A.B.); (M.S.)
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia;
| | - Mehdi Shakibaei
- Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilian-University Munich, 80336 Munich, Germany; (A.B.); (M.S.)
| | - Dietrich Büsselberg
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar;
- Correspondence: ; Tel.: +974-4492-8334
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Ruiz de Porras V, Layos L, Martínez-Balibrea E. Curcumin: A therapeutic strategy for colorectal cancer? Semin Cancer Biol 2020; 73:321-330. [PMID: 32942023 DOI: 10.1016/j.semcancer.2020.09.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 08/26/2020] [Accepted: 09/05/2020] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is the second cause of cancer death worldwide. The metastatic disease is mainly treated with aggressive therapies consisting on combinations of cytotoxic chemotherapy plus anti-EGFR or anti-VEGF drugs. In spite of the improvements in clinical outcomes achieved in the last decade, these are the result of multiple new combinations using the existing therapeutic options and the introduction of regorafenib and TAS-102 in second or later lines of treatment. As immunotherapies are limited to less than 5% of CRC patients harboring tumors with deficient mismatch repair, there is an urgent need of finding new drugs to increase our patients' survival opportunities. Among all the natural products that are candidates to be used for the treatment of CRC cancer, curcumin (the golden spice) is in the spotlight. Used for centuries in the Ayurveda medicine, its demonstrated anticancer properties and low toxicity profile made it the focus of hundreds of preclinical and clinical investigations. So far we know that it can be combined with most of the aforementioned drugs in a safe and synergistic way. Regretfully, its poor bioavailability has been one of the main issues for its successful introduction in the clinic. Nevertheless, a plethora of new formulations with a huge increase in bioavailability are under study with promising results. In this review we discuss the possibility of incorporating curcumin in the treatment of CRC; specifically, we review preclinical and clinical data supporting its possible combination with current therapies as well as new formulations under clinical study. It is time for the golden spice revolution.
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Affiliation(s)
- Vicenç Ruiz de Porras
- B-ARGO Group, Medical Oncology Service, Catalan Institute of Oncology, Ctra. Del Canyet s/n, 08916, Badalona, Spain; Germans Trias i Pujol Research Institute (IGTP), Ctra. De Can Ruti, camí de les escoles s/n, 08916, Badalona, Spain.
| | - Laura Layos
- B-ARGO Group, Medical Oncology Service, Catalan Institute of Oncology, Ctra. Del Canyet s/n, 08916, Badalona, Spain; Germans Trias i Pujol Research Institute (IGTP), Ctra. De Can Ruti, camí de les escoles s/n, 08916, Badalona, Spain; Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Ctra. De Can Ruti, camí de les escoles s/n, 08916, Badalona, Spain.
| | - Eva Martínez-Balibrea
- Germans Trias i Pujol Research Institute (IGTP), Ctra. De Can Ruti, camí de les escoles s/n, 08916, Badalona, Spain; Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Ctra. De Can Ruti, camí de les escoles s/n, 08916, Badalona, Spain; Program of Predictive and Personalized Cancer Medicine (PMPPC), IGTP, Ctra. De Can Ruti, camí de les escoles s/n, 08916, Badalona, Spain.
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45
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Wang F, Su H, Lin R, Chakroun RW, Monroe MK, Wang Z, Porter M, Cui H. Supramolecular Tubustecan Hydrogel as Chemotherapeutic Carrier to Improve Tumor Penetration and Local Treatment Efficacy. ACS NANO 2020; 14:10083-10094. [PMID: 32806082 DOI: 10.1021/acsnano.0c03286] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Local chemotherapy is a clinically proven strategy in treating malignant brain tumors. Its benefits, however, are largely limited by the rapid release and clearance of therapeutic agents and the inability to penetrate through tumor tissues. We report here on a supramolecular tubustecan (TT) hydrogel as both a therapeutic and drug carrier that enables long-term, sustained drug release and improved tumor tissue penetration. Covalent linkage of a tissue penetrating cyclic peptide to two camptothecin drug units creates a TT prodrug amphiphile that can associate into tubular supramolecular polymers and subsequently form a well-defined sphere-shaped hydrogel after injection into tumor tissues. The hollow nature of the resultant tubular assemblies allows for encapsulation of doxorubicin or curcumin for combination therapy. Our in vitro and in vivo studies reveal that these dual drug-bearing supramolecular hydrogels enhance tumor retention and penetration, serving as a local therapeutic depot for potent tumor regression, inhibition of tumor metastasis and recurrence, and mitigation of the off-target side effects.
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Affiliation(s)
- Feihu Wang
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Institute for NanoBiotechnology (INBT), Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Hao Su
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Institute for NanoBiotechnology (INBT), Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Ran Lin
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Institute for NanoBiotechnology (INBT), Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Rami W Chakroun
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Institute for NanoBiotechnology (INBT), Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Maya K Monroe
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Institute for NanoBiotechnology (INBT), Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Zongyuan Wang
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Institute for NanoBiotechnology (INBT), Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Michael Porter
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Institute for NanoBiotechnology (INBT), Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Honggang Cui
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Institute for NanoBiotechnology (INBT), Johns Hopkins University, Baltimore, Maryland 21218, United States
- Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
- Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
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46
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Nahari G, Braitbard O, Larush L, Hochman J, Tshuva EY. Effective Oral Administration of an Antitumorigenic Nanoformulated Titanium Complex. ChemMedChem 2020; 16:108-112. [PMID: 32657024 DOI: 10.1002/cmdc.202000384] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Indexed: 12/13/2022]
Abstract
Orally administered anticancer drugs facilitate treatment, but the acidic conditions in the stomach often challenge their availability. PhenolaTi is a TiIV -based nontoxic anticancer drug with marked in-vivo efficacy. We report that nanoformulation protects phenolaTi from decomposition in stomach-like conditions. This is evidenced by similar NMR characteristics and similar in-vitro cytotoxicity toward murine (CT-26) and human (HT-29) colon cancer cells before and after incubation of nanoformulated phenolaTi (phenolaTi-F) at pH 2, unlike results with the unformulated form of the complex. Furthermore, administration of phenolaTi-F in animal drinking water revealed a notable inhibition of tumor growth in Balb/c and immune-deficient (Nude) mice inoculated with CT-26 and HT-29 cells, respectively. In-vivo efficacy was at least similar to that of the corresponding intraperitoneal treatment with phenolaTi-F and the clinically employed oral drug, capecitabine. No body weight loss or clinical signs of toxicity were evident in the phenolaTi-F-treated animals. These findings demonstrate a new convenient mode of cancer treatment through oral administration by safe titanium-based drugs.
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Affiliation(s)
- Gilad Nahari
- The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel
| | - Ori Braitbard
- Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel
| | - Liraz Larush
- The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel
| | - Jacob Hochman
- Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel
| | - Edit Y Tshuva
- The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel
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47
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Khatoon E, Banik K, Harsha C, Sailo BL, Thakur KK, Khwairakpam AD, Vikkurthi R, Devi TB, Gupta SC, Kunnumakkara AB. Phytochemicals in cancer cell chemosensitization: Current knowledge and future perspectives. Semin Cancer Biol 2020; 80:306-339. [DOI: 10.1016/j.semcancer.2020.06.014] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 06/11/2020] [Accepted: 06/12/2020] [Indexed: 02/07/2023]
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48
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Henamayee S, Banik K, Sailo BL, Shabnam B, Harsha C, Srilakshmi S, VGM N, Baek SH, Ahn KS, Kunnumakkara AB. Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties. Molecules 2020; 25:molecules25102278. [PMID: 32408623 PMCID: PMC7288145 DOI: 10.3390/molecules25102278] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 05/02/2020] [Accepted: 05/07/2020] [Indexed: 12/19/2022] Open
Abstract
According to the World Health Organization (WHO), cancer is the second-highest cause of mortality in the world, and it kills nearly 9.6 million people annually. Besides the fatality of the disease, poor prognosis, cost of conventional therapies, and associated side-effects add more burden to patients, post-diagnosis. Therefore, the search for alternatives for the treatment of cancer that are safe, multi-targeted, effective, and cost-effective has compelled us to go back to ancient systems of medicine. Natural herbs and plant formulations are laden with a variety of phytochemicals. One such compound is rhein, which is an anthraquinone derived from the roots of Rheum spp. and Polygonum multiflorum. In ethnomedicine, these plants are used for the treatment of inflammation, osteoarthritis, diabetes, and bacterial and helminthic infections. Increasing evidence suggests that this compound can suppress breast cancer, cervical cancer, colon cancer, lung cancer, ovarian cancer, etc. in both in vitro and in vivo settings. Recent studies have reported that this compound modulates different signaling cascades in cancer cells and can prevent angiogenesis and progression of different types of cancers. The present review highlights the cancer-preventing and therapeutic properties of rhein based on the available literature, which will help to extend further research to establish the chemoprotective and therapeutic roles of rhein compared to other conventional drugs. Future pharmacokinetic and toxicological studies could support this compound as an effective anticancer agent.
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Affiliation(s)
- Sahu Henamayee
- Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Assam 781039, India; (S.H.); (K.B.); (B.L.S.); (B.S.); (C.H.)
| | - Kishore Banik
- Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Assam 781039, India; (S.H.); (K.B.); (B.L.S.); (B.S.); (C.H.)
| | - Bethsebie Lalduhsaki Sailo
- Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Assam 781039, India; (S.H.); (K.B.); (B.L.S.); (B.S.); (C.H.)
| | - Bano Shabnam
- Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Assam 781039, India; (S.H.); (K.B.); (B.L.S.); (B.S.); (C.H.)
| | - Choudhary Harsha
- Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Assam 781039, India; (S.H.); (K.B.); (B.L.S.); (B.S.); (C.H.)
| | - Satti Srilakshmi
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER, Guwahati), Assam 781125, India; (S.S.); (N.V.)
| | - Naidu VGM
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER, Guwahati), Assam 781125, India; (S.S.); (N.V.)
| | - Seung Ho Baek
- College of Korean Medicine, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Korea;
| | - Kwang Seok Ahn
- Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
- Correspondence: (K.S.A.); or (A.B.K.); Tel.: +82-2-961-2316 (K.S.A.)
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Assam 781039, India; (S.H.); (K.B.); (B.L.S.); (B.S.); (C.H.)
- Correspondence: (K.S.A.); or (A.B.K.); Tel.: +82-2-961-2316 (K.S.A.)
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Chen L, Cheng MM, Li YP, Lin SF, Zheng QH, Liu QY. 4,4'‑Bond secalonic acid D targets SP cells and inhibits metastasis in hepatocellular carcinoma. Mol Med Rep 2020; 21:2624-2632. [PMID: 32323850 DOI: 10.3892/mmr.2020.11055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 03/06/2020] [Indexed: 12/24/2022] Open
Abstract
The existence of cancer stem cells (CSCs) is considered to be the main reason for chemoresistance, metastasis and the ultimate failure of treatment in hepatocellular carcinoma (HCC). However, there are a few chemical agents that may inhibit CSCs. The present study identified that 4,4'‑bond secalonic acid D (4,4'‑SAD), a compound isolated from the marine‑derived fungus Penicillium oxalicum, inhibited the growth of side population (SP) cells isolated from human liver cancer cell lines PLC/PRF/5 and HuH‑7 by attenuating the expression of ATP‑binding cassette superfamily G member 2. Furthermore, the results of wound healing, Transwell, western blotting and reverse transcription‑quantitative PCR assays demonstrated that 4,4'‑SAD suppressed the invasion and migration of SP cells by downregulating matrix metallopeptidase 9 (MMP‑9) and upregulating the antagonist tissue inhibitor of metalloproteinases 1 in vitro. Moreover, in vivo study results found that 4,4'‑SAD had anti‑lung metastasis efficacy via the decrease of MMP‑9 expression in the H22 HCC model of Kunming mice. Therefore, the present study identified the potential of 4,4'‑SAD as a promising candidate for the treatment of advanced liver cancer.
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Affiliation(s)
- Li Chen
- Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, P.R. China
| | - Miao-Miao Cheng
- Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou, Fujian 350002, P.R. China
| | - Ya-Ping Li
- Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou, Fujian 350002, P.R. China
| | - Shao-Feng Lin
- Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, P.R. China
| | - Qiu-Hong Zheng
- Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, P.R. China
| | - Qin-Ying Liu
- Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, P.R. China
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50
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Curcumin and colorectal cancer: An update and current perspective on this natural medicine. Semin Cancer Biol 2020; 80:73-86. [PMID: 32088363 PMCID: PMC7438305 DOI: 10.1016/j.semcancer.2020.02.011] [Citation(s) in RCA: 152] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 02/10/2020] [Accepted: 02/17/2020] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is one of most common malignancies worldwide and its incidence is still growing. In spite of recent advances in targeted therapies, their clinical efficacy has been limited, non-curative and unaffordable. A growing body of literature indicates that CRC is a multi-modal disease, where a variety of factors within the tumor microenvironment play a significant role in its pathogenesis. For instance, imbalance in gut microbial profiles and impaired intestinal barrier function contribute to the overall intestinal inflammation and initiation of CRC. Moreover, persistent chronic inflammation favors a tumor microenvironment for the growth of cancer. In addition, autophagy or 'self-eating' is a surveillance mechanism involved in the degradation of cellular constituents that are generated under stressful conditions. Cancer stem cells (CSCs), on the other hand, engage in the onset of CRC and are able to endow cancer cells with chemo-resistance. Furthermore, the aberrant epigenetic alterations promote CRC. These evidences highlight the need for multi-targeted approaches that are not only safe and inexpensive but offer a more effective alternative to current generation of targeted drugs. Curcumin, derived from the plant Curcuma longa, represents one such option that has a long history of its use for a variety of chronic disease including cancer, in Indian ayurvedic and traditional Chinese medicine. Scientific evidence over the past few decades have overwhelmingly shown that curcumin exhibits a multitude of anti-cancer activities orchestrated through key signaling pathways associated with cancer. In this article, we will present a current update and perspective on this natural medicine - incorporating the basic cellular mechanisms it effects and the current state of clinical evidence, challenges and promise for its use as a cancer preventative and potential adjunct together with modern therapies for CRC patients.
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