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Filippi A, Deculescu-Ioniță T, Hudiță A, Baldasici O, Gălățeanu B, Mocanu MM. Molecular Mechanisms of Dietary Compounds in Cancer Stem Cells from Solid Tumors: Insights into Colorectal, Breast, and Prostate Cancer. Int J Mol Sci 2025; 26:631. [PMID: 39859345 PMCID: PMC11766403 DOI: 10.3390/ijms26020631] [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: 11/21/2024] [Revised: 01/10/2025] [Accepted: 01/11/2025] [Indexed: 01/27/2025] Open
Abstract
Cancer stem cells (CSC) are known to be the main source of tumor relapse, metastasis, or multidrug resistance and the mechanisms to counteract or eradicate them and their activity remain elusive. There are different hypotheses that claim that the origin of CSC might be in regular stem cells (SC) and, due to accumulation of mutations, these normal cells become malignant, or the source of CSC might be in any malignant cell that, under certain environmental circumstances, acquires all the qualities to become CSC. Multiple studies indicate that lifestyle and diet might represent a source of wellbeing that can prevent and ameliorate the malignant phenotype of CSC. In this review, after a brief introduction to SC and CSC, we analyze the effects of phenolic and non-phenolic dietary compounds and we highlight the molecular mechanisms that are shown to link diets to CSC activation in colon, breast, and prostate cancer. We focus the analysis on specific markers such as sphere formation, CD surface markers, epithelial-mesenchymal transition (EMT), Oct4, Nanog, Sox2, and aldehyde dehydrogenase 1 (ALDH1) and on the major signaling pathways such as PI3K/Akt/mTOR, NF-κB, Notch, Hedgehog, and Wnt/β-catenin in CSC. In conclusion, a better understanding of how bioactive compounds in our diets influence the dynamics of CSC can raise valuable awareness towards reducing cancer risk.
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Affiliation(s)
- Alexandru Filippi
- Department of Biochemistry and Biophysics, “Carol Davila” University of Medicine and Pharmacy of Bucharest, 050474 Bucharest, Romania;
| | - Teodora Deculescu-Ioniță
- Department of Pharmacognosy, Phytochemistry and Phytotherapy, “Carol Davila” University of Medicine and Pharmacy of Bucharest, 050474 Bucharest, Romania;
| | - Ariana Hudiță
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (A.H.); (B.G.)
| | - Oana Baldasici
- Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuță”, 400015 Cluj-Napoca, Romania;
| | - Bianca Gălățeanu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (A.H.); (B.G.)
| | - Maria-Magdalena Mocanu
- Department of Biochemistry and Biophysics, “Carol Davila” University of Medicine and Pharmacy of Bucharest, 050474 Bucharest, Romania;
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2
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Sumaira S, Vijayarathna S, Hemagirri M, Adnan M, Hassan MI, Patel M, Gupta R, Shanmugapriya, Chen Y, Gopinath SC, Kanwar JR, Sasidharan S. Plant bioactive compounds driven microRNAs (miRNAs): A potential source and novel strategy targeting gene and cancer therapeutics. Noncoding RNA Res 2024; 9:1140-1158. [PMID: 39022680 PMCID: PMC11250886 DOI: 10.1016/j.ncrna.2024.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/21/2024] [Accepted: 06/03/2024] [Indexed: 07/20/2024] Open
Abstract
Irrespective of medical technology improvements, cancer ranks among the leading causes of mortality worldwide. Although numerous cures and treatments exist, creating alternative cancer therapies with fewer adverse side effects is vital. Since ancient times, plant bioactive compounds have already been used as a remedy to heal cancer. These plant bioactive compounds and their anticancer activity can also deregulate the microRNAs (miRNAs) in the cancerous cells. Therefore, the deregulation of miRNAs in cancer cells by plant bioactive compounds and the usage of the related miRNA could be a promising approach for cancer cure, mainly to prevent cancer and overcome chemotherapeutic side effect problems. Hence, this review highlights the function of plant bioactive compounds as an anticancer agent through the underlying mechanism that alters the miRNA expression in cancer cells, ultimately leading to apoptosis. Moreover, this review provides insight into using plant bioactive compounds -driven miRNAs as an anticancer agent to develop miRNA-based cancer gene therapy. They can be the potential resource for gene therapy and novel strategies targeting cancer therapeutics.
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Affiliation(s)
- Sahreen Sumaira
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM, 11800, Pulau Pinang, Malaysia
| | - Soundararajan Vijayarathna
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM, 11800, Pulau Pinang, Malaysia
| | - Manisekaran Hemagirri
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM, 11800, Pulau Pinang, Malaysia
| | - Mohd Adnan
- Department of Biology, College of Science, University of Hail, Hail, P.O. Box 2440, Saudi Arabia
| | - Md Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India
| | - Mitesh Patel
- Research and Development Cell and Department of Biotechnology, Parul Institute of Applied Sciences, Parul University, Vadodara, 391760, Gujarat, India
| | - Reena Gupta
- Institute of Pharmaceutical Research, Department. Pharmaceutical Research, GLA University, Mathura, India
| | - Shanmugapriya
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM, 11800, Pulau Pinang, Malaysia
| | - Yeng Chen
- Department of Oral & Craniofacial Sciences, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Subash C.B. Gopinath
- Faculty of Chemical Engineering Technology, Universiti Malaysia Perlis, Perlis, Malaysia
| | - Jagat R. Kanwar
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), 174001, Bilaspur, Himachal Pradesh, India
| | - Sreenivasan Sasidharan
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM, 11800, Pulau Pinang, Malaysia
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3
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Wang Q, Huang H, Yang Y, Yang X, Li X, Zhong W, Wen B, He F, Li J. Reinventing gut health: leveraging dietary bioactive compounds for the prevention and treatment of diseases. Front Nutr 2024; 11:1491821. [PMID: 39502877 PMCID: PMC11534667 DOI: 10.3389/fnut.2024.1491821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 10/07/2024] [Indexed: 11/08/2024] Open
Abstract
The human gut harbors a complex and diverse microbiota essential for maintaining health. Diet is the most significant modifiable factor influencing gut microbiota composition and function, particularly through bioactive compounds like polyphenols, dietary fibers, and carotenoids found in vegetables, fruits, seafood, coffee, and green tea. These compounds regulate the gut microbiota by promoting beneficial bacteria and suppressing harmful ones, leading to the production of key microbiota-derived metabolites such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. These metabolites are crucial for gut homeostasis, influencing gut barrier function, immune responses, energy metabolism, anti-inflammatory processes, lipid digestion, and modulation of gut inflammation. This review outlines the regulatory impact of typical bioactive compounds on the gut microbiota and explores the connection between specific microbiota-derived metabolites and overall health. We discuss how dietary interventions can affect disease development and progression through mechanisms involving these metabolites. We examine the roles of bioactive compounds and their metabolites in the prevention and treatment of diseases including inflammatory bowel disease, colorectal cancer, cardiovascular diseases, obesity, and type 2 diabetes mellitus. This study provides new insights into disease prevention and underscores the potential of dietary modulation of the gut microbiota as a strategy for improving health.
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Affiliation(s)
- Qiurong Wang
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Hui Huang
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Ying Yang
- Chengdu Medical College, Chengdu, China
| | - Xianglan Yang
- Pengzhou Branch of the First Affiliated Hospital of Chengdu Medical College, Pengzhou Second People’s Hospital, Chengdu, China
| | - Xuemei Li
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Wei Zhong
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Biao Wen
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Feng He
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Jun Li
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
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Andrade EDS, Santos RA, Guillermo LVC, Miyoshi N, Ferraz da Costa DC. Immunomodulatory Effects of Green Tea Catechins and Their Ring Fission Metabolites in a Tumor Microenvironment Perspective. Molecules 2024; 29:4575. [PMID: 39407505 PMCID: PMC11478201 DOI: 10.3390/molecules29194575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 09/24/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
Green tea is the second most consumed beverage following water, and the health benefits provided by its consumption have been well established from research in recent decades. The main bioactive compounds found in all Camellia sinensis-based teas are catechins, which have been reported to have antioxidant, anticancer, anti-inflammatory, and immunomodulatory properties. Although most of the health benefits are well established, studies show that the intact catechins as found in tea are poorly absorbed in the digestive tract. These compounds are degraded and undergo ring fission by the gut microbiota, increasing their absorption. In this review, we gather knowledge of the health benefits of green tea catechins and their metabolites, with a particular emphasis on the immunomodulatory effects in a cancer microenvironment scenario.
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Affiliation(s)
- Emmanuele D. S. Andrade
- Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan;
- Laboratory of Pathophysiology and Biochemistry of Nutrition, Department of Basic and Experimental Nutrition, Institute of Nutrition, Rio de Janeiro State University/UERJ, Rio de Janeiro 20550-013, Brazil;
| | - Ronimara A. Santos
- Laboratory of Pathophysiology and Biochemistry of Nutrition, Department of Basic and Experimental Nutrition, Institute of Nutrition, Rio de Janeiro State University/UERJ, Rio de Janeiro 20550-013, Brazil;
| | - Landi V. C. Guillermo
- Laboratory of Investigation on Mechanisms of Immunoregulation, Department of Microbiology and Parasitology, Biomedical Institute, Federal State University of Rio de Janeiro/UNIRIO, Rio de Janeiro 22290-240, Brazil;
| | - Noriyuki Miyoshi
- Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan;
| | - Danielly C. Ferraz da Costa
- Laboratory of Pathophysiology and Biochemistry of Nutrition, Department of Basic and Experimental Nutrition, Institute of Nutrition, Rio de Janeiro State University/UERJ, Rio de Janeiro 20550-013, Brazil;
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Almaraz-Postigo S, Sanz E, Pandiella A, Díaz-Rodríguez E. Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer. Nutrients 2024; 16:2416. [PMID: 39125297 PMCID: PMC11313973 DOI: 10.3390/nu16152416] [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: 06/18/2024] [Revised: 07/19/2024] [Accepted: 07/24/2024] [Indexed: 08/12/2024] Open
Abstract
Ovarian cancer is the most fatal of all the reproductive cancers within the female population, mainly due to its late diagnosis that limits surgery and medical treatment. Classically, ovarian cancer therapy has included conventional chemotherapy, and other therapeutic approaches are now being used to treat these patients, but the outcomes of the disease are still poor. Therefore, new strategies are needed to improve life expectancy and life quality of ovarian cancer patients. Considering that, we investigated the effect of the nutritional supplement Ocoxin Oral Solution (OOS) in ovarian cancer models. OOS contains several nutritional supplements, some of them with demonstrated antitumoral action. In vitro studies showed that OOS inhibited the proliferation of several ovarian cancer cell lines, especially of those representative of the endometrioid subtype, in a time- and dose-dependent manner. A fast cell death induction after OOS treatment was observed, and when the molecular mechanisms leading to this effect were investigated, an activation of the DNA damage checkpoint was detected, as shown by activation (phosphorylation) of CHK1 and CHK2 kinases that was followed by the phosphorylation of the target protein histone H2AX. When tested in animal models of ovarian cancer, OOS reduced tumor growth without any observed secondary effects. Moreover, such reduction in tumor proliferation was caused by the induction of DNA damage as corroborated by the in vivo phosphorylation of CHK2 and Histone H2AX. Finally, OOS potentiated the action of carboplatin or olaparib, the standard of care treatments used in ovarian clinics, opening the possibility of including OOS in combination with those standard of care agents in patients with ovarian cancer.
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Affiliation(s)
- Sheila Almaraz-Postigo
- Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Investigación Biomédica de Salamanca (IBSAL) and Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Campus Miguel de Unamuno, 37007 Salamanca, Spain; (S.A.-P.); (A.P.)
| | | | - Atanasio Pandiella
- Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Investigación Biomédica de Salamanca (IBSAL) and Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Campus Miguel de Unamuno, 37007 Salamanca, Spain; (S.A.-P.); (A.P.)
| | - Elena Díaz-Rodríguez
- Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Investigación Biomédica de Salamanca (IBSAL) and Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Campus Miguel de Unamuno, 37007 Salamanca, Spain; (S.A.-P.); (A.P.)
- Department of Biochemistry, Universidad de Salamanca, 37008 Salamanca, Spain
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Yang J, Sun Q, Liu X, Yang Y, Rong R, Yan P, Xie Y. Targeting Notch signaling pathways with natural bioactive compounds: a promising approach against cancer. Front Pharmacol 2024; 15:1412669. [PMID: 39092224 PMCID: PMC11291470 DOI: 10.3389/fphar.2024.1412669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 06/27/2024] [Indexed: 08/04/2024] Open
Abstract
Notch signaling pathway is activated abnormally in solid and hematological tumors, which perform essential functions in cell differentiation, survival, proliferation, and angiogenesis. The activation of Notch signaling and communication among Notch and other oncogenic pathways heighten malignancy aggressiveness. Thus, targeting Notch signaling offers opportunities for improved survival and reduced disease incidence. Already, most attention has been given to its role in the cancer cells. Recent research shows that natural bioactive compounds can change signaling molecules that are linked to or interact with the Notch pathways. This suggests that there may be a link between Notch activation and the growth of tumors. Here, we sum up the natural bioactive compounds that possess inhibitory effects on human cancers by impeding the Notch pathway and preventing Notch crosstalk with other oncogenic pathways, which provoke further study of these natural products to derive rational therapeutic regimens for the treatment of cancer and develop novel anticancer drugs. This review revealed Notch as a highly challenging but promising target in oncology.
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Affiliation(s)
- Jia Yang
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Qihui Sun
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaoyun Liu
- Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Yong Yang
- Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Rong Rong
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China
| | - Peiyu Yan
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China
| | - Ying Xie
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
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Barathan M, Zulpa AK, Ng SL, Lokanathan Y, Ng MH, Law JX. Innovative Strategies to Combat 5-Fluorouracil Resistance in Colorectal Cancer: The Role of Phytochemicals and Extracellular Vesicles. Int J Mol Sci 2024; 25:7470. [PMID: 39000577 PMCID: PMC11242358 DOI: 10.3390/ijms25137470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 07/04/2024] [Accepted: 07/05/2024] [Indexed: 07/16/2024] Open
Abstract
Colorectal cancer (CRC) is a significant public health challenge, with 5-fluorouracil (5-FU) resistance being a major obstacle to effective treatment. Despite advancements, resistance to 5-FU remains formidable due to complex mechanisms such as alterations in drug transport, evasion of apoptosis, dysregulation of cell cycle dynamics, tumor microenvironment (TME) interactions, and extracellular vesicle (EV)-mediated resistance pathways. Traditional chemotherapy often results in high toxicity, highlighting the need for alternative approaches with better efficacy and safety. Phytochemicals (PCs) and EVs offer promising CRC therapeutic strategies. PCs, derived from natural sources, often exhibit lower toxicity and can target multiple pathways involved in cancer progression and drug resistance. EVs can facilitate targeted drug delivery, modulate the immune response, and interact with the TME to sensitize cancer cells to treatment. However, the potential of PCs and engineered EVs in overcoming 5-FU resistance and reshaping the immunosuppressive TME in CRC remains underexplored. Addressing this gap is crucial for identifying innovative therapies with enhanced efficacy and reduced toxicities. This review explores the multifaceted mechanisms of 5-FU resistance in CRC and evaluates the synergistic effects of combining PCs with 5-FU to improve treatment efficacy while minimizing adverse effects. Additionally, it investigates engineered EVs in overcoming 5-FU resistance by serving as drug delivery vehicles and modulating the TME. By synthesizing the current knowledge and addressing research gaps, this review enhances the academic understanding of 5-FU resistance in CRC, highlighting the potential of interdisciplinary approaches involving PCs and EVs for revolutionizing CRC therapy. Further research and clinical validation are essential for translating these findings into improved patient outcomes.
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Affiliation(s)
- Muttiah Barathan
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia
| | - Ahmad Khusairy Zulpa
- Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Sook Luan Ng
- Department of Craniofacial Diagnostics and Biosciences, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia
| | - Yogeswaran Lokanathan
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia
| | - Min Hwei Ng
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia
| | - Jia Xian Law
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia
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Hon KW, Naidu R. Synergistic Mechanisms of Selected Polyphenols in Overcoming Chemoresistance and Enhancing Chemosensitivity in Colorectal Cancer. Antioxidants (Basel) 2024; 13:815. [PMID: 39061884 PMCID: PMC11273411 DOI: 10.3390/antiox13070815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/29/2024] [Accepted: 07/03/2024] [Indexed: 07/28/2024] Open
Abstract
Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Despite significant advances in medical treatment, chemotherapy as monotherapy can lead to substantial side effects and chemoresistance. This underscores the need for therapeutic approaches that are not only pharmacologically safe but also modulate multiple potent signaling pathways and sensitize cancer cells to overcome resistance to standard drugs. In recent years, scientists have been searching for natural compounds that can be used as chemosensitizers in addition to conventional medications for the synergistic treatment of CRC. Polyphenols represent a diverse group of natural compounds that can target multiple signaling pathways in cancer cells to induce anti-cancer effects. Additionally, polyphenols have been shown to work synergistically with chemotherapeutics and other natural compounds in cancer cells. This review aims to provide a comprehensive insight into the synergistic mechanisms of selected polyphenols as chemosensitizers in CRC cells. Further research and clinical trials are warranted to fully harness the synergistic mechanisms of selected polyphenols combined with chemotherapy or natural compounds in improving cancer treatment outcomes.
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Affiliation(s)
| | - Rakesh Naidu
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor Darul Ehsan, Malaysia;
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Okpoghono J, Isoje EF, Igbuku UA, Ekayoda O, Omoike GO, Adonor TO, Igue UB, Okom SU, Ovowa FO, Stephen-Onojedje QO, Ejueyitsi EO, Seigha AA. Natural polyphenols: A protective approach to reduce colorectal cancer. Heliyon 2024; 10:e32390. [PMID: 38961927 PMCID: PMC11219337 DOI: 10.1016/j.heliyon.2024.e32390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 06/01/2024] [Accepted: 06/03/2024] [Indexed: 07/05/2024] Open
Abstract
Background A form of cancer that affects the rectum or colon (large intestine) is called colorectal cancer (CRC). The main risk factors for CRC include dietary, lifestyle, and environmental variables. Currently natural polyphenols have demonstrated impressive anticarcinogenic capabilities. Objective The main objective was to provide an updated, thorough assessment of the defensive mechanism of natural polyphenols for the global suppression of colorectal cancer. More precisely, this study aimed to analyze a set of chosen polyphenols with demonstrated safety, effectiveness, and biochemical defense mechanism on colon cancer models in order to facilitate future research. Methods This review was carried out with purposefully attentive and often updated scientific databases, including PubMed, Scopus, Science Direct, and Web of Science. After selecting approximately 178 potentially relevant papers based just on abstracts, 145 studies were meticulously reviewed and discussed. Results The outcomes disclosed that anti-CRC mechanisms of natural polyphenols involved the control of several molecular and signaling pathways. Natural polyphenols have also been shown to have the ability to limit the growth and genesis of tumors via altering the gut microbiota and cancer stem cells. However, the biochemical uses of many natural polyphenols have remained restricted because of their truncated water solubility and low bioavailability. In order to attain synergistic properties it is recommended to combine the use of different natural polyphenols because of their low bioavailability and volatility. However, the use of lipid-based nano- and micro-carriers also may be helpful to solve these problems with efficient distribution system to target sites. Conclusion In conclusion, the use of polyphenols for CRC treatment appears promising. To ascertain their efficacy, more clinical research is anticipated.
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Affiliation(s)
- Joel Okpoghono
- Department of Biochemistry, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Endurance F. Isoje
- Department of Science Laboratory Technology (Biochemistry Option), Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Ufuoma A. Igbuku
- Department of Chemistry, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Ovigueroye Ekayoda
- Department of Biochemistry, Faculty of Science, Delta State University, Abraka, Delta State, Nigeria
| | - Godson O. Omoike
- Department of Public Health, School of Health and Society, University of Wolverhampton, United Kingdom
| | - Treasure O. Adonor
- Department of Biotechnology, Faculty of Life Science, University of Essex, United Kingdom
| | - Udoka B. Igue
- Department of Chemical Sciences, Novena University, Ogume, Delta State, Nigeria
| | - Solomon U. Okom
- Department of Biochemistry, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Faith O. Ovowa
- Department of Science Laboratory Technology (Biochemistry Option), Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Queen O. Stephen-Onojedje
- Department of Biochemistry, Faculty of Science, Delta State University, Abraka, Delta State, Nigeria
| | - Ejiro O. Ejueyitsi
- Department of Biochemistry, Faculty of Science, Delta State University, Abraka, Delta State, Nigeria
| | - Anita A. Seigha
- Department of Chemical Sciences, Novena University, Ogume, Delta State, Nigeria
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10
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Masci D, Puxeddu M, Silvestri R, La Regina G. Metabolic Rewiring in Cancer: Small Molecule Inhibitors in Colorectal Cancer Therapy. Molecules 2024; 29:2110. [PMID: 38731601 PMCID: PMC11085455 DOI: 10.3390/molecules29092110] [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: 03/15/2024] [Revised: 04/16/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Alterations in cellular metabolism, such as dysregulation in glycolysis, lipid metabolism, and glutaminolysis in response to hypoxic and low-nutrient conditions within the tumor microenvironment, are well-recognized hallmarks of cancer. Therefore, understanding the interplay between aerobic glycolysis, lipid metabolism, and glutaminolysis is crucial for developing effective metabolism-based therapies for cancer, particularly in the context of colorectal cancer (CRC). In this regard, the present review explores the complex field of metabolic reprogramming in tumorigenesis and progression, providing insights into the current landscape of small molecule inhibitors targeting tumorigenic metabolic pathways and their implications for CRC treatment.
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Affiliation(s)
- Domiziana Masci
- Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy;
| | - Michela Puxeddu
- Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy; (M.P.); (R.S.)
| | - Romano Silvestri
- Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy; (M.P.); (R.S.)
| | - Giuseppe La Regina
- Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy; (M.P.); (R.S.)
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11
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Rauf A, Joshi PB, Olatunde A, Hafeez N, Ahmad Z, Hemeg HA, Aljohani ASM, Al Abdulmonem W, Thiruvengadam M, Viswanathan D, Rajakumar G, Thiruvengadam R. Comprehensive review of the repositioning of non-oncologic drugs for cancer immunotherapy. Med Oncol 2024; 41:122. [PMID: 38652344 DOI: 10.1007/s12032-024-02368-8] [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: 01/22/2024] [Accepted: 03/20/2024] [Indexed: 04/25/2024]
Abstract
Drug repositioning or repurposing has gained worldwide attention as a plausible way to search for novel molecules for the treatment of particular diseases or disorders. Drug repurposing essentially refers to uncovering approved or failed compounds for use in various diseases. Cancer is a deadly disease and leading cause of mortality. The search for approved non-oncologic drugs for cancer treatment involved in silico modeling, databases, and literature searches. In this review, we provide a concise account of the existing non-oncologic drug molecules and their therapeutic potential in chemotherapy. The mechanisms and modes of action of the repurposed drugs using computational techniques are also highlighted. Furthermore, we discuss potential targets, critical pathways, and highlight in detail the different challenges pertaining to drug repositioning for cancer immunotherapy.
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Affiliation(s)
- Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, 23561, Khyber Pakhtunkhwa, Pakistan
| | - Payal B Joshi
- Operations and Method Development, Shefali Research Laboratories, Ambernath, Maharashtra, 421501, India
| | - Ahmed Olatunde
- Department of Medical Biochemistry, Abubakar Tafawa Balewa University, Bauchi, 740272, Nigeria
| | - Nabia Hafeez
- Center of Biotechnology and Microbiology, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan
| | - Zubair Ahmad
- Department of Chemistry, University of Swabi, Anbar, 23561, Khyber Pakhtunkhwa, Pakistan
| | - Hassan A Hemeg
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, P.O. Box 344, Al-Medinah, Al-Monawara, Saudi Arabia
| | - Abdullah S M Aljohani
- Department of Medical Biosciences, College of Veterinary Medicine, Qassim University, 52571, Buraydah, Saudi Arabia
| | - Waleed Al Abdulmonem
- Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Muthu Thiruvengadam
- Department of Applied Bioscience, College of Life and Environmental Science, Konkuk University, Seoul, 05029, Republic of Korea
| | - Dhivya Viswanathan
- Center for NanoBioscience, Department of Orthodontics, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospitals, Saveetha University, Chennai, Tamil Nadu, 600077, India
| | - Govindasamy Rajakumar
- Center for NanoBioscience, Department of Orthodontics, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospitals, Saveetha University, Chennai, Tamil Nadu, 600077, India.
| | - Rekha Thiruvengadam
- Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, 600077, India.
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12
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Dharshini LCP, Mandal AKA. Regulation of gene expression by modulating microRNAs through Epigallocatechin-3-gallate in cancer. Mol Biol Rep 2024; 51:230. [PMID: 38281210 DOI: 10.1007/s11033-023-09145-2] [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: 11/09/2023] [Accepted: 12/12/2023] [Indexed: 01/30/2024]
Abstract
Cancer is an intricate ailment that has a higher death rate globally and is characterized by aberrant cell proliferation and metastasis in nature. Since the beginning of healthcare, natural products, especially those derived from plants, have been utilized to support human health. Green tea contains an essential catechin called epigallocatechin gallate, which has anti-proliferative, anti-mutagenic, anti-inflammatory, and antioxidative properties. The anticancer properties of EGCG have been extensively studied using pre-clinical cell culture and animal model systems. Dysregulated miRNA may be a biomarker since it influences the different characteristics of cancer like upholding proliferative signaling, cell death, invasiveness, metastasis, and angiogenesis. EGCG either elevates or lowers the expression of dysregulated miRNAs in cancer. Nonetheless, due to its anticancer properties, greater attention has been paid towards the development of efficient strategies for utilizing EGCG in cancer chemotherapy. This review summarizes the modifying effect of EGCG on miRNAs in cancer after briefly discussing the anticancer mechanisms of EGCG and the function of miRNAs in cancer.
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Affiliation(s)
| | - Abul Kalam Azad Mandal
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
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13
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Tripathi T, Yadav J, Janjua D, Chaudhary A, Joshi U, Senrung A, Chhokar A, Aggarwal N, Bharti AC. Targeting Cervical Cancer Stem Cells by Phytochemicals. Curr Med Chem 2024; 31:5222-5254. [PMID: 38288813 DOI: 10.2174/0109298673281823231222065616] [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: 09/12/2023] [Revised: 11/25/2023] [Accepted: 11/30/2023] [Indexed: 09/06/2024]
Abstract
Cervical cancer (CaCx) poses a significant global health challenge, ranking as the fourth most common cancer among women worldwide. Despite the emergence of advanced treatment strategies, recurrence remains a bottleneck in favorable treatment outcomes and contributes to poor prognosis. The chemo- or radio-therapy resistance coupled with frequent relapse of more aggressive tumors are some key components that contribute to CaCx-related mortality. The onset of therapy resistance and relapse are attributed to a small subset of, slow-proliferating Cancer Stem Cells (CSC). These CSCs possess the properties of tumorigenesis, self-renewal, and multi-lineage differentiation potential. Because of slow cycling, these cells maintain themselves in a semi-quiescent stage and protect themselves from different anti-proliferative anti-cancer drugs. Keeping in view recent advances in their phenotypic and functional characterization, the feasibility of targeting CSC and associated stem cell signaling bears a strong translational value. The presence of CSC has been reported in CaCx (CCSC) which remains a forefront area of research. However, we have yet to identify clinically useful leads that can target CCSC. There is compelling evidence that phytochemicals, because of their advantages over synthetic anticancer drugs, could emerge as potential therapeutic leads to target these CCSCs. The present article examined the potential of phytochemicals with reported anti-CSC properties and evaluated their future in preclinical and clinical applications against CaCx.
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Affiliation(s)
- Tanya Tripathi
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), Delhi, 110007, India
| | - Joni Yadav
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), Delhi, 110007, India
| | - Divya Janjua
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), Delhi, 110007, India
| | - Apoorva Chaudhary
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), Delhi, 110007, India
| | - Udit Joshi
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), Delhi, 110007, India
| | - Anna Senrung
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), Delhi, 110007, India
- Neuropharmacology and Drug Delivery Laboratory, Department of Zoology, Daulat Ram College, University of Delhi (North Campus), Delhi, 110007, India
| | - Arun Chhokar
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), Delhi, 110007, India
- Deshbandhu College, University of Delhi, New Delhi, 110019, India
| | - Nikita Aggarwal
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), Delhi, 110007, India
| | - Alok Chandra Bharti
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), Delhi, 110007, India
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14
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Chaudhuri R, Samanta A, Saha P, Ghosh S, Sinha D. The Potential of Epigallocatechin Gallate in Targeting Cancer Stem Cells: A Comprehensive Review. Curr Med Chem 2024; 31:5255-5280. [PMID: 38243984 DOI: 10.2174/0109298673281666231227053726] [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: 09/13/2023] [Revised: 11/17/2023] [Accepted: 11/30/2023] [Indexed: 01/22/2024]
Abstract
The dreadful scenario of cancer prevails due to the presence of cancer stem cells (CSCs), which contribute to tumor growth, metastasis, invasion, resistance to chemo- and radiotherapy, and recurrence. CSCs are a small subpopulation of cells within the tumor that are characterized by self-renewal capability and have the potential to manifest heterogeneous lineages of cancer cells that constitute the tumor. The major bioactive green tea polyphenol (-)-epigallocatechin gallate (EGCG) has been fruitful in downgrading cancer stemness signaling and CSC biomarkers in cancer progression. EGCG has been evidenced to maneuver extrinsic and intrinsic apoptotic pathways in order to decrease the viability of CSCs. Cancer stemness is intricately related to epithelial-mesenchymal transition (EMT), metastasis and therapy resistance, and EGCG has been evidenced to regress all these CSC-related effects. By inhibiting CSC characteristics EGCG has also been evidenced to sensitize the tumor cells to radiotherapy and chemotherapy. However, the use of EGCG in in vitro and in vivo cancer models raises concern about its bioavailability, stability and efficacy against spheroids raised from parental cells. Therefore, novel nano formulations of EGCG and adjuvant therapy of EGCG with other phytochemicals or drugs or small molecules may have a better prospect in targeting CSCs. However, extensive clinical research is still awaited to elucidate a full proof impact of EGCG in cancer therapy.
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Affiliation(s)
- Rupa Chaudhuri
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, 700026, India
| | - Anurima Samanta
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, 700026, India
| | - Priyanka Saha
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, 700026, India
| | - Sukanya Ghosh
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, 700026, India
| | - Dona Sinha
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, 700026, India
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15
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Ajmeera D, Ajumeera R. Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance. Genes Dis 2024; 11:148-175. [PMID: 37588226 PMCID: PMC10425757 DOI: 10.1016/j.gendis.2022.12.013] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 11/21/2022] [Accepted: 12/08/2022] [Indexed: 01/21/2023] Open
Abstract
Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments. Novel strategies are therefore required for better management of cancer therapy. The prime approach would be to synthesize and develop novel drugs that need extensive resources, time, and endurance to be brought into therapeutic use. The subsequent approach would be to screen the anti-cancer activity of available non-cancerous drugs. This concept of repurposing non-cancer drugs as an alternative to current cancer therapy has become popular in recent years because using existing anticancer drugs has several adverse effects. Micronutrients have also been investigated for cancer therapy due to their significant anti-cancer effects with negligible or no side effects and availability in food sources. In this paper, we discuss an ideal hypothesis for screening available non-cancerous drugs with anticancer activity, with a focus on cancer stem cells and their clinical application for cancer treatment. Further, drug repurposing and the combination of micronutrients that can target both cancers and cancer stem cells may result in a better therapeutic approach leading to maximum tumor growth control.
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Affiliation(s)
- Divya Ajmeera
- Cell Biology Department, ICMR-National Institute of Nutrition (NIN), Hyderabad, Telangana 500007, India
| | - Rajanna Ajumeera
- Cell Biology Department, ICMR-National Institute of Nutrition (NIN), Hyderabad, Telangana 500007, India
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16
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Zhao H, Han R, Wang Z, Xian J, Bai X. Colorectal Cancer Stem Cells and Targeted Agents. Pharmaceutics 2023; 15:2763. [PMID: 38140103 PMCID: PMC10748092 DOI: 10.3390/pharmaceutics15122763] [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: 10/13/2023] [Revised: 11/30/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
Since their discovery, cancer stem cells have become a hot topic in cancer therapy research. These cells possess stem cell-like self-renewal and differentiation capacities and are important factors that dominate cancer metastasis, therapy-resistance and recurrence. Worse, their inherent characteristics make them difficult to eliminate. Colorectal cancer is the third-most common cancer and the second leading cause of cancer death worldwide. Targeting colorectal cancer stem cells (CR-CSCs) can inhibit colorectal cancer metastasis, enhance therapeutic efficacy and reduce recurrence. Here, we introduced the origin, biomarker proteins, identification, cultivation and research techniques of CR-CSCs, and we summarized the signaling pathways that regulate the stemness of CR-CSCs, such as Wnt, JAK/STAT3, Notch and Hh signaling pathway. In addition to these, we also reviewed recent anti-CR-CSC drugs targeting signaling pathways, biomarkers and other regulators. These will help researchers gain insight into the current agents targeting to CR-CSCs, explore new cancer drugs and propose potential therapies.
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Affiliation(s)
- Haobin Zhao
- Department of General Practice, People’s Hospital of Longhua, 38 Jinglong Jianshe Road, Shenzhen 518109, China; (H.Z.); (J.X.)
- Endocrinology Department, People’s Hospital of Longhua, 38 Jinglong Jianshe Road, Shenzhen 518109, China
| | - Ruining Han
- Obstetric Department, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518033, China;
| | - Zhankun Wang
- Emergency Department, People’s Hospital of Longhua, 38 Jinglong Jianshe Road, Shenzhen 518109, China;
| | - Junfang Xian
- Department of General Practice, People’s Hospital of Longhua, 38 Jinglong Jianshe Road, Shenzhen 518109, China; (H.Z.); (J.X.)
| | - Xiaosu Bai
- Endocrinology Department, People’s Hospital of Longhua, 38 Jinglong Jianshe Road, Shenzhen 518109, China
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17
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Proença C, Freitas M, Ribeiro D, Rufino AT, Fernandes E, Ferreira de Oliveira JMP. The role of flavonoids in the regulation of epithelial-mesenchymal transition in cancer: A review on targeting signaling pathways and metastasis. Med Res Rev 2023; 43:1878-1945. [PMID: 37147865 DOI: 10.1002/med.21966] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 03/20/2023] [Accepted: 04/12/2023] [Indexed: 05/07/2023]
Abstract
One of the hallmarks of cancer is metastasis, a process that entails the spread of cancer cells to distant regions in the body, culminating in tumor formation in secondary organs. Importantly, the proinflammatory environment surrounding cancer cells further contributes to cancer cell transformation and extracellular matrix destruction. During metastasis, front-rear polarity and emergence of migratory and invasive features are manifestations of epithelial-mesenchymal transition (EMT). A variety of transcription factors (TFs) are implicated in the execution of EMT, the most prominent belonging to the Snail Family Transcriptional Repressor (SNAI) and Zinc Finger E-Box Binding Homeobox (ZEB) families of TFs. These TFs are regulated by interaction with specific microRNAs (miRNAs), as miR34 and miR200. Among the several secondary metabolites produced in plants, flavonoids constitute a major group of bioactive molecules, with several described effects including antioxidant, antiinflammatory, antidiabetic, antiobesogenic, and anticancer effects. This review scrutinizes the modulatory role of flavonoids on the activity of SNAI/ZEB TFs and on their regulatory miRNAs, miR-34, and miR-200. The modulatory role of flavonoids can attenuate mesenchymal features and stimulate epithelial features, thereby inhibiting and reversing EMT. Moreover, this modulation is concomitant with the attenuation of signaling pathways involved in diverse processes as cell proliferation, cell growth, cell cycle progression, apoptosis inhibition, morphogenesis, cell fate, cell migration, cell polarity, and wound healing. The antimetastatic potential of these versatile compounds is emerging and represents an opportunity for the synthesis of more specific and potent agents.
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Affiliation(s)
- Carina Proença
- LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Marisa Freitas
- LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Daniela Ribeiro
- LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Ana T Rufino
- LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Eduarda Fernandes
- LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - José Miguel P Ferreira de Oliveira
- LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
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18
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Mahanti K, Bhattacharyya S. Rough neighborhood: Intricacies of cancer stem cells and infiltrating immune cell interaction in tumor microenvironment and potential in therapeutic targeting. Transl Res 2023; 265:S1931-5244(23)00176-7. [PMID: 39491179 DOI: 10.1016/j.trsl.2023.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 10/25/2023] [Accepted: 10/25/2023] [Indexed: 11/05/2024]
Abstract
Ongoing research on cellular heterogeneity of Cancer stem cells (CSCs) and its synergistic involvement with tumor milieu reveals enormous complexity, resulting in diverse hindrance in immune therapy. CSCs has captured attention for their contribution in shaping of tumor microenvironment and as target for therapeutic intervention. Recent studies have highlighted cell-extrinsic and intrinsic mechanisms of reciprocal interaction between tumor stroma constituents and CSCs. Therapeutic targeting requires an in-depth understanding of the underlying mechanisms involved with the rate limiting factors in tumor aggressiveness and pinpoint role of CSCs. Some of the major constituents of tumor microenvironment includes resident and infiltrating immune cell, both innate and adaptive. Some of these immune cells play crucial role as adjustors of tumor immune response. Tumor-adjustor immune cell interaction confer plasticity and features enabling tumor growth and metastasis in one hand and on the other hand blunts anti-tumor immunity. Detail understanding of CSC and TME resident immune cells interaction can shape new avenues for cancer immune therapy. In this review, we have tried to summarize the development of knowledge on cellular, molecular and functional interaction between CSCs and tumor microenvironment immune cells, highlighting immune-mediated therapeutic strategies aimed at CSCs. We also discussed developing a potential CSC and TME targeted therapeutic avenue.
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Affiliation(s)
- Krishna Mahanti
- Immunobiology and Translational medicine laboratory, Department of Zoology, Sidho Kanho Birsha University, Purulia, 723104, West Bengal India
| | - Sankar Bhattacharyya
- Immunobiology and Translational medicine laboratory, Department of Zoology, Sidho Kanho Birsha University, Purulia, 723104, West Bengal India.
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19
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Wang C, Bai M, Sun Z, Yao N, Zhang A, Guo S, Asemi Z. Epigallocatechin-3-gallate and cancer: focus on the role of microRNAs. Cancer Cell Int 2023; 23:241. [PMID: 37838685 PMCID: PMC10576883 DOI: 10.1186/s12935-023-03081-8] [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: 07/26/2023] [Accepted: 09/21/2023] [Indexed: 10/16/2023] Open
Abstract
MicroRNAs (miRNAs) are a group of small non-coding RNAs that affect gene expression. The role of miRNAs in different types of cancers has been published and it was shown that several miRNAs are inappropriately expressed in different cancers. Among the mechanisms that can cause this lack of proper expression are epigenetics, chromosomal changes, polymorphisms or defects in processing proteins. Recent research shows that phytochemicals, including epigallocatechin-3-gallate (EGCG), exert important epigenetic-based anticancer effects such as pro-apoptotic or anti proliferative through miRNA gene silencing. Given that EGCG is able to modulate a variety of cancer-related process i.e., angiogenesis, proliferation, metastasis and apoptosis via targeting various miRNAs such as let-7, miR-16, and miR-210. The discovery of new miRNAs and the differences observed in their expression when exposed to EGCG provides evidence that targeting these miRNAs may be beneficial as a form of treatment. In this review, we aim to provide an overview, based on current knowledge, on how phytochemicals, including epigallocatechin-3-gallate, can be considered as potential miRNAs modulator to improve efficacy of current cancer treatments.
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Affiliation(s)
- Chunguang Wang
- The First Affiliated Hospital of Hebei North University, Zhang Jiakou, 075000, Hebei, China
| | - Meiling Bai
- Basic Medical College of Hebei North University, Zhang Jiakou, 075000, Hebei, China.
| | - Zhiguang Sun
- The First Affiliated Hospital of Hebei North University, Zhang Jiakou, 075000, Hebei, China
| | - Nan Yao
- The First Affiliated Hospital of Hebei North University, Zhang Jiakou, 075000, Hebei, China
| | - Aiting Zhang
- The First Affiliated Hospital of Hebei North University, Zhang Jiakou, 075000, Hebei, China
| | - Shengyu Guo
- The First Affiliated Hospital of Hebei North University, Zhang Jiakou, 075000, Hebei, China
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran.
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20
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Şahin TÖ, Yılmaz B, Yeşilyurt N, Cicia D, Szymanowska A, Amero P, Ağagündüz D, Capasso R. Recent insights into the nutritional immunomodulation of cancer-related microRNAs. Phytother Res 2023; 37:4375-4397. [PMID: 37434291 DOI: 10.1002/ptr.7937] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 06/21/2023] [Accepted: 06/24/2023] [Indexed: 07/13/2023]
Abstract
Cancer is the most common cause of death worldwide, following cardiovascular diseases. Cancer is a multifactorial disease and many reasons such as physical, chemical, biological, and lifestyle-related factors. Nutrition, which is one of the various factors that play a role in the prevention, development, and treatment of many types of cancer, affects the immune system, which is characterized by disproportionate pro-inflammatory signaling in cancer. Studies investigating the molecular mechanisms of this effect have shown that foods rich in bioactive compounds, such as green tea, olive oil, turmeric, and soybean play a significant role in positively changing the expression of miRNAs involved in the regulation of genes associated with oncogenic/tumor-suppressing pathways. In addition to these foods, some diet models may change the expression of specific cancer-related miRNAs in different ways. While Mediterranean diet has been associated with anticancer effects, a high-fat diet, and a methyl-restricted diet are considered to have negative effects. This review aims to discuss the effects of specific foods called "immune foods," diet models, and bioactive components on cancer by changing the expression of miRNAs in the prevention and treatment of cancer.
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Affiliation(s)
| | - Birsen Yılmaz
- Department of Nutrition and Dietetics, Cukurova University, Adana, Turkey
| | | | - Donatella Cicia
- Department of Pharmacy, University of Naples Federico II, Napoli, Italy
| | - Anna Szymanowska
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Paola Amero
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Duygu Ağagündüz
- Department of Nutrition and Dietetics, Gazi University, Ankara, Turkey
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, Napoli, Italy
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21
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Roshani M, Molavizadeh D, Sadeghi S, Jafari A, Dashti F, Mirazimi SMA, Ahmadi Asouri S, Rajabi A, Hamblin MR, Anoushirvani AA, Mirzaei H. Emerging roles of miR-145 in gastrointestinal cancers: A new paradigm. Biomed Pharmacother 2023; 166:115264. [PMID: 37619484 DOI: 10.1016/j.biopha.2023.115264] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 07/25/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
Gastrointestinal (GI) carcinomas are a group of cancers affecting the GI tract and digestive organs, such as the gastric, liver, bile ducts, pancreas, small intestine, esophagus, colon, and rectum. MicroRNAs (miRNAs) are small functional non-coding RNAs (ncRNAs) which are involved in regulating the expression of multiple target genes; mainly at the post-transcriptional level, via complementary binding to their 3'-untranslated region (3'-UTR). Increasing evidence has shown that miRNAs have critical roles in modulating of various physiological and pathological cellular processes and regulating the occurrence and development of human malignancies. Among them, miR-145 is recognized for its anti-oncogenic properties in various cancers, including GI cancers. MiR-145 has been implicated in diverse biological processes of cancers through the regulation of target genes or signaling, including, proliferation, differentiation, tumorigenesis, angiogenesis, apoptosis, metastasis, and therapy resistance. In this review, we have summarized the role of miR-145 in selected GI cancers and also its downstream molecules and cellular processes targets, which could lead to a better understanding of the miR-145 in these cancers. In conclusion, we reveal the potential diagnostic, prognostic, and therapeutic value of miR-145 in GI cancer, and hope to provide new ideas for its application as a biomarker as well as a therapeutic target for the treatment of these cancer.
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Affiliation(s)
- Mohammad Roshani
- Internal Medicine and Gastroenterology, Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Danial Molavizadeh
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Sara Sadeghi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Ameneh Jafari
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Dashti
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Seyed Mohammad Ali Mirazimi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Sahar Ahmadi Asouri
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for BasicSciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Ali Rajabi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Ali Arash Anoushirvani
- Department of Internal Medicine, Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Hamed Mirzaei
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Internal Medicine, Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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22
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Andrade KHS, Coelho JAS, Frade R, Madureira AM, Nunes JPM, Caddick S, Gomes RFA, Afonso CAM. Functionalized Cyclopentenones with Low Electrophilic Character as Anticancer Agents. ChemMedChem 2023; 18:e202300104. [PMID: 37062707 DOI: 10.1002/cmdc.202300104] [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: 02/22/2023] [Revised: 04/10/2023] [Accepted: 04/13/2023] [Indexed: 04/18/2023]
Abstract
In this study were synthesized non-Michael acceptor cyclopentenones (CP) from biomass derivative furfural as anticancer agents. Cyclic enones, both from natural sources and synthetic analogues, have been described as cytotoxic agents. Most of these agents were unsuccessful in becoming valuable therapeutic agents due to toxicity problems derived from unselective critical biomacromolecule alkylation. This may be caused by Michael addition to the enone system. Ab initio studies revealed that 2,4-substituted CPs are less prone to Michael additions, and as such were tested three families of those derivatives. We prepare the new CPs from furfural through a tandem furan ring opening/Nazarov electrocyclization and further functionalization. Experimentally the 2,4-substituted CPs exhibited no reactivity towards sulphur nucleophiles, while maintaining cytotoxicity against HT-29, MCF-7, NCI-H460, HCT-116 and MDA-MB 231 cells lines. Moreover, the selected CP are non-toxic against healthy HEK 293T cell lines and present proper calculated drug-like properties.
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Affiliation(s)
- Késsia H S Andrade
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisboa, Portugal
| | - Jaime A S Coelho
- Centro de Química Estrutural, Institute of Molecular Sciences, Faculty of Sciences, University of Lisbon, 1749-016, Lisboa, Portugal
| | - Raquel Frade
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisboa, Portugal
| | - Ana M Madureira
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisboa, Portugal
| | - João P M Nunes
- Abzena Ltd., Babraham Research Campus, Cambridge, CB22 3AT, UK
- Department of Chemistry, University College London, London, WC1H 0AJ, UK
| | - Stephen Caddick
- Department of Chemistry, University College London, London, WC1H 0AJ, UK
| | - Rafael F A Gomes
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisboa, Portugal
- CBIOS-Universidade Lusófona's Research Center for Biosciences & Health Technologies, Universidade Lusófona, Lisboa, 1749-024, Lisboa, Portugal
| | - Carlos A M Afonso
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisboa, Portugal
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23
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Cianciosi D, Armas Diaz Y, Alvarez-Suarez JM, Chen X, Zhang D, Martínez López NM, Briones Urbano M, Quiles JL, Amici A, Battino M, Giampieri F. Can the phenolic compounds of Manuka honey chemosensitize colon cancer stem cells? A deep insight into the effect on chemoresistance and self-renewal. Food Chem 2023; 427:136684. [PMID: 37418807 DOI: 10.1016/j.foodchem.2023.136684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 06/14/2023] [Accepted: 06/18/2023] [Indexed: 07/09/2023]
Abstract
Manuka honey, which is rich in pinocembrin, quercetin, naringenin, salicylic, p-coumaric, ferulic, syringic and 3,4-dihydroxybenzoic acids, has been shown to have pleiotropic effects against colon cancer cells. In this study, potential chemosensitizing effects of Manuka honey against 5-Fluorouracil were investigated in colonspheres enriched with cancer stem cells (CSCs), which are responsible for chemoresistance. Results showed that 5-Fluorouracil increased when it was combined with Manuka honey by downregulating the gene expression of both ATP-binding cassette sub-family G member 2, an efflux pump and thymidylate synthase, the main target of 5-Fluorouracil which regulates the ex novo DNA synthesis. Manuka honey was associated with decreased self-renewal ability by CSCs, regulating expression of several genes in Wnt/β-catenin, Hedgehog and Notch pathways. This preliminary study opens new areas of research into the effects of natural compounds in combination with pharmaceuticals and, potentially, increase efficacy or reduce adverse effects.
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Affiliation(s)
- Danila Cianciosi
- Dipartimento di Scienze Cliniche Specialistiche e Odontostomatologiche - Università Politecnica delle Marche, Via Ranieri 65, 60130 Ancona, Italy
| | - Yasmany Armas Diaz
- Dipartimento di Scienze Cliniche Specialistiche e Odontostomatologiche - Università Politecnica delle Marche, Via Ranieri 65, 60130 Ancona, Italy
| | - José M Alvarez-Suarez
- Departamento de Ingeniería en Alimentos. Colegio de Ciencias e Ingenierías, Universidad San Francisco de Quito, Diego de Robles s/n, Quito 170901, Ecuador
| | - Xiumin Chen
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; Institute of Food Physical Processing, Jiangsu University, Zhenjiang 212013, China; International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing, Jiangsu University, Zhenjiang 212013, China
| | - Di Zhang
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Nohora Milena Martínez López
- Universidad Internacional Iberoamericana, Campeche 24560, Mexico; Fundación Universitaria Internacional de Colombia, Bogotá, Colombia; Universidad Internacional Iberoamericana Arecibo, Puerto Rico 00613, USA
| | - Mercedes Briones Urbano
- Universidad Europea del Atlántico, 39011 Santander, Spain; Universidad Internacional Iberoamericana, Campeche 24560, Mexico; Universidad Internacional Iberoamericana Arecibo, Puerto Rico 00613, USA
| | - José L Quiles
- Department of Physiology, Institute of Nutrition and Food Technology "José Mataix", Biomedical Research Center, University of Granada, Avda del Conocimiento s/n, Parque Tecnologico de la Salud, Armilla, 18016 Granada, Spain; Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres, 21, Santander 39011, Spain; Research and Development Functional Food Centre (CIDAF), Health Science Technological Park, Avenida del Conocimiento 37, Granada 18016, Spain
| | - Adolfo Amici
- Dipartimento di Scienze Cliniche Specialistiche e Odontostomatologiche - Università Politecnica delle Marche, Via Ranieri 65, 60130 Ancona, Italy
| | - Maurizio Battino
- Dipartimento di Scienze Cliniche Specialistiche e Odontostomatologiche - Università Politecnica delle Marche, Via Ranieri 65, 60130 Ancona, Italy; International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing, Jiangsu University, Zhenjiang 212013, China; Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres, 21, Santander 39011, Spain.
| | - Francesca Giampieri
- Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres, 21, Santander 39011, Spain.
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24
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Farhan M. Insights on the Role of Polyphenols in Combating Cancer Drug Resistance. Biomedicines 2023; 11:1709. [PMID: 37371804 PMCID: PMC10296548 DOI: 10.3390/biomedicines11061709] [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: 05/22/2023] [Revised: 06/10/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Chemotherapy resistance is still a serious problem in the treatment of most cancers. Many cellular and molecular mechanisms contribute to both inherent and acquired drug resistance. They include the use of unaffected growth-signaling pathways, changes in the tumor microenvironment, and the active transport of medicines out of the cell. The antioxidant capacity of polyphenols and their potential to inhibit the activation of procarcinogens, cancer cell proliferation, metastasis, and angiogenesis, as well as to promote the inhibition or downregulation of active drug efflux transporters, have been linked to a reduced risk of cancer in epidemiological studies. Polyphenols also have the ability to alter immunological responses and inflammatory cascades, as well as trigger apoptosis in cancer cells. The discovery of the relationship between abnormal growth signaling and metabolic dysfunction in cancer cells highlights the importance of further investigating the effects of dietary polyphenols, including their ability to boost the efficacy of chemotherapy and avoid multidrug resistance (MDR). Here, it is summarized what is known regarding the effectiveness of natural polyphenolic compounds in counteracting the resistance that might develop to cancer drugs as a result of a variety of different mechanisms.
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Affiliation(s)
- Mohd Farhan
- Department of Basic Sciences, Preparatory Year Deanship, King Faisal University, Al Ahsa 31982, Saudi Arabia
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25
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Wang L, Li P, Feng K. EGCG adjuvant chemotherapy: Current status and future perspectives. Eur J Med Chem 2023; 250:115197. [PMID: 36780831 DOI: 10.1016/j.ejmech.2023.115197] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 02/07/2023] [Accepted: 02/08/2023] [Indexed: 02/12/2023]
Abstract
The resistance of cancer cells to chemotherapeutic drugs greatly reduces the therapeutic effect in cancer patients, and the toxic side effects caused by chemotherapy also seriously affect the quality of life of patients. The combination of epigallocatechin-3-gallate (EGCG), the main active ingredient in tea, with cisplatin, 5-FU, doxorubicin and paclitaxel enhances their sensitizing effect on tumors and combats the drug resistance of cancer cells. These effects seem to be mediated by a variety of mechanisms, including combating drug resistance mediated by cancer stem cells, enhancing drug sensitivity, inducing cell cycle arrest and apoptosis, and blocking angiogenesis. In addition, EGCG can suppress a series of adverse effects caused by chemotherapy, such as gastrointestinal disorders, nephrotoxicity and cardiotoxicity, through its anti-inflammatory and antioxidant effects and improve the quality of life of patients. However, the low bioavailability and off-target effects of EGCG and its reactivity with some chemotherapeutic agents limit its clinical application. The nanomodification of EGCG and chemotherapeutic drugs not only enhances the antitumor activity but also prolongs the survival time of tumor-bearing mice, and has the advantage of low toxicity. Therefore, this review aims to discuss the current status and challenges regarding the use of EGCG in combination with chemotherapy drugs in the treatment of cancer. In general, EGCG is a promising adjuvant for chemotherapy.
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Affiliation(s)
- Lin Wang
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen, 518118, Guangdong, China
| | - Penghui Li
- Center for Health Research, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, Guangdong, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Kun Feng
- Pingshan District People's Hospital of Shenzhen, Pingshan General Hospital of Southern Medical University, Shenzhen, 518118, Guangdong, China.
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26
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Costa AR, Duarte AC, Costa-Brito AR, Gonçalves I, Santos CRA. Bitter taste signaling in cancer. Life Sci 2023; 315:121363. [PMID: 36610638 DOI: 10.1016/j.lfs.2022.121363] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/21/2022] [Accepted: 12/30/2022] [Indexed: 01/06/2023]
Abstract
Pharmacoresistance of cancer cells to many drugs used in chemotherapy remains a major challenge for the treatment of cancer. Multidrug resistance transporters, especially ATP-binding cassette (ABC) transporters, are a major cause of cancer drug resistance since they translocate a broad range of drug compounds across the cell membrane, extruding them out of the cells. The regulation of ABC transporters by bitter taste receptors (TAS2Rs), which might be activated by specific bitter tasting compounds, was described in several types of cells/organs, becoming a potential target for cancer therapy. TAS2Rs expression has been reported in many organs and several types of cancer, like breast, ovarian, prostate, and colorectal cancers, where their activation was shown to be involved in various biological actions (cell survival, apoptosis, molecular transport, among others). Moreover, many TAS2Rs' ligands, such as flavonoids and alkaloids, with well-recognized beneficial properties, including several anticancer effects, have been reported as potential adjuvants in cancer therapies. In this review, we discuss the potential therapeutic role of TAS2Rs and bitter tasting compounds in different types of cancer as a possible way to circumvent chemoresistance.
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Affiliation(s)
- Ana R Costa
- CICS-UBI - Health Sciences Research Centre, Universidade da Beira Interior, Covilhã, Portugal
| | - Ana C Duarte
- CICS-UBI - Health Sciences Research Centre, Universidade da Beira Interior, Covilhã, Portugal; CPIRN-IPG - Centro de Potencial e Inovação de Recursos Naturais, Instituto Politécnico da Guarda, Guarda, Portugal
| | - Ana R Costa-Brito
- CICS-UBI - Health Sciences Research Centre, Universidade da Beira Interior, Covilhã, Portugal; Research Unit for Inland Development (UDI), Polytechnic of Guarda, Guarda, Portugal
| | - Isabel Gonçalves
- CICS-UBI - Health Sciences Research Centre, Universidade da Beira Interior, Covilhã, Portugal
| | - Cecília R A Santos
- CICS-UBI - Health Sciences Research Centre, Universidade da Beira Interior, Covilhã, Portugal.
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27
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De S, Paul S, Manna A, Majumder C, Pal K, Casarcia N, Mondal A, Banerjee S, Nelson VK, Ghosh S, Hazra J, Bhattacharjee A, Mandal SC, Pal M, Bishayee A. Phenolic Phytochemicals for Prevention and Treatment of Colorectal Cancer: A Critical Evaluation of In Vivo Studies. Cancers (Basel) 2023; 15:993. [PMID: 36765950 PMCID: PMC9913554 DOI: 10.3390/cancers15030993] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/30/2023] [Accepted: 01/30/2023] [Indexed: 02/08/2023] Open
Abstract
Colorectal cancer (CRC) is the third most diagnosed and second leading cause of cancer-related death worldwide. Limitations with existing treatment regimens have demanded the search for better treatment options. Different phytochemicals with promising anti-CRC activities have been reported, with the molecular mechanism of actions still emerging. This review aims to summarize recent progress on the study of natural phenolic compounds in ameliorating CRC using in vivo models. This review followed the guidelines of the Preferred Reporting Items for Systematic Reporting and Meta-Analysis. Information on the relevant topic was gathered by searching the PubMed, Scopus, ScienceDirect, and Web of Science databases using keywords, such as "colorectal cancer" AND "phenolic compounds", "colorectal cancer" AND "polyphenol", "colorectal cancer" AND "phenolic acids", "colorectal cancer" AND "flavonoids", "colorectal cancer" AND "stilbene", and "colorectal cancer" AND "lignan" from the reputed peer-reviewed journals published over the last 20 years. Publications that incorporated in vivo experimental designs and produced statistically significant results were considered for this review. Many of these polyphenols demonstrate anti-CRC activities by inhibiting key cellular factors. This inhibition has been demonstrated by antiapoptotic effects, antiproliferative effects, or by upregulating factors responsible for cell cycle arrest or cell death in various in vivo CRC models. Numerous studies from independent laboratories have highlighted different plant phenolic compounds for their anti-CRC activities. While promising anti-CRC activity in many of these agents has created interest in this area, in-depth mechanistic and well-designed clinical studies are needed to support the therapeutic use of these compounds for the prevention and treatment of CRC.
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Affiliation(s)
- Samhita De
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | - Sourav Paul
- Department of Biotechnology, National Institute of Technology, Durgapur 713 209, India
| | - Anirban Manna
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | | | - Koustav Pal
- Jawaharlal Institute Post Graduate Medical Education and Research, Puducherry 605 006, India
| | - Nicolette Casarcia
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Arijit Mondal
- Department of Pharmaceutical Chemistry, M.R. College of Pharmaceutical Sciences and Research, Balisha 743 234, India
| | - Sabyasachi Banerjee
- Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Asansol 713 301, India
| | - Vinod Kumar Nelson
- Department of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research, Anantapur 515 721, India
| | - Suvranil Ghosh
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | - Joyita Hazra
- Department of Biotechnology, Indian Institute of Technology, Chennai 600 036, India
| | - Ashish Bhattacharjee
- Department of Biotechnology, National Institute of Technology, Durgapur 713 209, India
| | | | - Mahadeb Pal
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
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28
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Tuli HS, Garg VK, Bhushan S, Uttam V, Sharma U, Jain A, Sak K, Yadav V, Lorenzo JM, Dhama K, Behl T, Sethi G. Natural flavonoids exhibit potent anticancer activity by targeting microRNAs in cancer: A signature step hinting towards clinical perfection. Transl Oncol 2023; 27:101596. [PMID: 36473401 PMCID: PMC9727168 DOI: 10.1016/j.tranon.2022.101596] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 11/15/2022] [Accepted: 11/26/2022] [Indexed: 12/12/2022] Open
Abstract
Cancer prevalence and its rate of incidence are constantly rising since the past few decades. Owing to the toxicity of present-day antineoplastic drugs, it is imperative to explore safer and more effective molecules to combat and/or prevent this dreaded disease. Flavonoids, a class of polyphenols, have exhibited multifaceted implications against several diseases including cancer, without showing significant toxicity towards the normal cells. Shredded pieces of evidence suggest that flavonoids can enhance drug sensitivity and suppress proliferation, metastasis, and angiogenesis of cancer cells by modulating several oncogenic or oncosuppressor microRNAs (miRNAs, miRs). They play pivotal roles in regulation of various biological and pathological processes, including various cancers. In the present review, the structure, chemistry and miR targeting efficacy of quercetin, luteolin, silibinin, genistein, epigallocatechin gallate, and cyanidin against several cancer types are comprehensively discussed. miRs are considered as next-generation medicine of recent times, and their targeting by naturally occurring flavonoids in cancer cells could be deemed as a signature step. We anticipate that our compilations related to miRNA-mediated regulation of cancer cells by flavonoids might catapult the clinical investigations and affirmation in the future.
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Affiliation(s)
- Hardeep Singh Tuli
- Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, 133207, India
| | - Vivek Kumar Garg
- Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Gharuan, Mohali, Punjab, 140413, India
| | - Sakshi Bhushan
- Department of Botany, Central University Jammu, Jammu and Kashmir 181143, India
| | - Vivek Uttam
- Department of Zoology, Central University of Punjab, Village-Ghudda, Punjab 151401, India
| | - Uttam Sharma
- Department of Zoology, Central University of Punjab, Village-Ghudda, Punjab 151401, India
| | - Aklank Jain
- Department of Zoology, Central University of Punjab, Village-Ghudda, Punjab 151401, India
| | | | - Vikas Yadav
- Department of Translational Medicine, Clinical Research Centre, Skåne University Hospital, Lund University, SE-20213 Malmö, Sweden
| | - Jose M Lorenzo
- Centro Tecnológico de la Carne de Galicia, Adva. Galicia n° 4, Parque Tecnológico de Galicia, San Cibrao das Viñas, Ourense 32900, Spain; Universidade de Vigo, Área de Tecnología de los Alimentos, Facultad de Ciencias de Ourense, 32004 Ourense, Spain
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh 243122, India
| | - Tapan Behl
- Department of Pharmacology, School of Health Sciences & Technology (SoHST), University of Petroleum and Energy Studies, Bidholi, Dehradun, Uttarakhand 248007, India.
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
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29
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Liao W, Zhang L, Chen X, Xiang J, Zheng Q, Chen N, Zhao M, Zhang G, Xiao X, Zhou G, Zeng J, Tang J. Targeting cancer stem cells and signalling pathways through phytochemicals: A promising approach against colorectal cancer. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 108:154524. [PMID: 36375238 DOI: 10.1016/j.phymed.2022.154524] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 10/10/2022] [Accepted: 10/24/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Cancer stem cells (CSCs) are strongly associated with high tumourigenicity, chemotherapy or radiotherapy resistance, and metastasis and recurrence, particularly in colorectal cancer (CRC). Therefore, targeting CSCs may be a promising approach. Recently, discovery and research on phytochemicals that effectively target colorectal CSCs have been gaining popularity because of their broad safety profile and multi-target and multi-pathway modes of action. PURPOSE This review aimed to elucidate and summarise the effects and mechanisms of phytochemicals with potential anti-CSC agents that could contribute to the better management of CRC. METHODS We reviewed PubMed, EMBASE, Web of Science, Ovid, ScienceDirect and China National Knowledge Infrastructure databases from the original publication date to March 2022 to review the mechanisms by which phytochemicals inhibit CRC progression by targeting CSCs and their key signalling pathways. Phytochemicals were classified and summarised based on the mechanisms of action. RESULTS We observed that phytochemicals could affect the biological properties of colorectal CSCs. Phytochemicals significantly inhibit self-renewal, migration, invasion, colony formation, and chemoresistance and induce apoptosis and differentiation of CSCs by regulating the Wnt/β-catenin pathway (e.g., diallyl trisulfide and genistein), the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway (e.g., caffeic acid and piperlongumine), the neurogenic locus notch homolog protein pathway (e.g., honokiol, quercetin, and α-mangostin), the Janus kinase-signal transducer and activator of transcription pathway (e.g., curcumin, morin, and ursolic acid), and other key signalling pathways. It is worth noting that several phytochemicals, such as resveratrol, silibinin, evodiamine, and thymoquinone, highlight multi-target and multi-pathway effects in restraining the malignant biological behaviour of CSCs. CONCLUSIONS This review demonstrates the potential of targeted therapies for colorectal CSCs using phytochemicals. Phytochemicals could serve as novel therapeutic agents for CRC and aid in drug development.
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Affiliation(s)
- Wenhao Liao
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Lanlan Zhang
- State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xian Chen
- Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Juyi Xiang
- Center for drug evaluation, National Medical Products Administration, Beijing 100022, China
| | - Qiao Zheng
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Nianzhi Chen
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Maoyuan Zhao
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Gang Zhang
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Xiaolin Xiao
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Gang Zhou
- Center for drug evaluation, National Medical Products Administration, Beijing 100022, China.
| | - Jinhao Zeng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
| | - Jianyuan Tang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
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30
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Zhang Y, Liu K, Yan C, Yin Y, He S, Qiu L, Li G. Natural Polyphenols for Treatment of Colorectal Cancer. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27248810. [PMID: 36557939 PMCID: PMC9787795 DOI: 10.3390/molecules27248810] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022]
Abstract
Colorectal cancer (CRC) is a prevalent and serious gastrointestinal malignancy with high mortality and morbidity. Chemoprevention refers to a newly emerged strategy that uses drugs with chemopreventive properties to promote antioxidation, regulate cancer cell cycle, suppress proliferation, and induce cellular apoptosis, so as to improve cancer treatment outcomes. Natural polyphenols are currently recognized as a class of chemopreventive agents that have shown remarkable anticarcinogenic properties. Numerous in vitro and in vivo studies have elucidated the anti-CRC mechanisms of natural polyphenols, such as regulation of various molecular and signaling pathways. Natural polyphenols are also reportedly capable of modulating the gut microbiota and cancer stem cells (CSCs) to suppress tumor formation and progression. Combined use of different natural polyphenols is recommended due to their low bioavailability and instability, and combination treatment can exert synergistical effects, reduce side effects, and avoid drug resistance in CRC treatment. In summary, the application of polyphenols in the chemoprevention and treatment of CRC is promising. Further clinical evaluation of their effectiveness is warranted and anticipated.
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Affiliation(s)
- Yiwen Zhang
- College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Kunjian Liu
- College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Chengqiu Yan
- Anorectal Department, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021, China
| | - Yu Yin
- College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Shuangyan He
- College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Li Qiu
- College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Guofeng Li
- Anorectal Department, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021, China
- Correspondence:
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31
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miR-145-5p Targets Sp1 in Non-Small Cell Lung Cancer Cells and Links to BMI1 Induced Pemetrexed Resistance and Epithelial-Mesenchymal Transition. Int J Mol Sci 2022; 23:ijms232315352. [PMID: 36499676 PMCID: PMC9741456 DOI: 10.3390/ijms232315352] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 12/01/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
Pemetrexed is a folic acid inhibitor used as a second-line chemotherapeutic agent for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), which accounts for 85% of lung cancers. However, prolonged treatment with pemetrexed may cause cancer cells to develop resistance. In this study, we found increased expressions of BMI1 (B Lymphoma Mo-MLV insertion region 1 homolog) and Sp1 and a decreased expression of miR-145-5p was found in pemetrexed-resistant A400 cells than in A549 cells. Direct Sp1 targeting activity of miR-145-5p was demonstrated by a luciferase based Sp1 3'-UTR reporter. Changed expression of miR-145-5p in A400 or A549 cells by transfection of miR-145-5p mimic or inhibitor affected the sensitivity of the cells to pemetrexed. On the other hand, the overexpression of Sp1 in A549 cells caused the decreased sensitivity to pemetrexed, induced cell migratory capability, and epithelial-mesenchymal transition (EMT) related transcription factors such as Snail Family Transcriptional Repressor 1 and Zinc Finger E-Box Binding Homeobox 1. In addition, the overexpression of BMI1 in the A549 cells resulted in an increase in Sp1 and a decrease in miR-145-5p accompanied by the elevations of cell proliferation and EMT transcription factors, which could be reduced by the overexpression of miR-145-5p or by treatment with the Sp1 inhibitor of mithramycin A. In conclusion, the results of this study suggest that the downregulation of miR-145-5p by BMI1 overexpression could lead to the enhanced expression of Sp1 to induce the EMT process in pemetrexed-resistant NSCLC cells. These results suggest that increasing miR-145-5p expression by delivering RNA drugs may serve as a sensitizing agent for pemetrexed-resistant NSCLC patients.
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Gor R, Ramachandran I, Ramalingam S. Targeting the Cancer Stem Cells in Endocrine Cancers with Phytochemicals. Curr Top Med Chem 2022; 22:2589-2597. [PMID: 36380414 DOI: 10.2174/1567205020666221114112814] [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: 06/19/2022] [Revised: 09/11/2022] [Accepted: 10/13/2022] [Indexed: 11/17/2022]
Abstract
Endocrine cancer is an uncontrolled growth of cells in the hormone-producing glands. Endocrine cancers include the adrenal, thyroid, parathyroid, pancreas, pituitary, and ovary malignancy. Recently, there is an increase in the incidence of the most common endocrine cancer types, namely pancreatic and thyroid cancers. Cancer stem cells (CSCs) of endocrine tumors have received more attention due to their role in cancer progression, therapeutic resistance, and cancer relapse. Phytochemicals provide several health benefits and are effective in the treatment of various diseases including cancer. Therefore, finding the natural phytochemicals that target the CSCs will help to improve cancer patients' prognosis and life expectancy. Phytochemicals have been shown to have anticancer properties and are very effective in treating various cancer types. Curcumin is a common polyphenol found in turmeric, which has been shown to promote cellular drug accumulation and increase the effectiveness of chemotherapy. Moreover, various other phytochemicals such as resveratrol, genistein, and apigenin are effective against different endocrine cancers by regulating the CSCs. Thus, phytochemicals have emerged as chemotherapeutics that may have significance in preventing and treating the endocrine cancers.
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Affiliation(s)
- Ravi Gor
- Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, 603203, Tamil Nadu, India
| | - Ilangovan Ramachandran
- Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, Tamil Nadu, India
| | - Satish Ramalingam
- Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, 603203, Tamil Nadu, India
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Hayakawa S, Ohishi T, Oishi Y, Isemura M, Miyoshi N. Contribution of Non-Coding RNAs to Anticancer Effects of Dietary Polyphenols: Chlorogenic Acid, Curcumin, Epigallocatechin-3-Gallate, Genistein, Quercetin and Resveratrol. Antioxidants (Basel) 2022; 11:antiox11122352. [PMID: 36552560 PMCID: PMC9774417 DOI: 10.3390/antiox11122352] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/18/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Growing evidence has been accumulated to show the anticancer effects of daily consumption of polyphenols. These dietary polyphenols include chlorogenic acid, curcumin, epigallocatechin-3-O-gallate, genistein, quercetin, and resveratrol. These polyphenols have similar chemical and biological properties in that they can act as antioxidants and exert the anticancer effects via cell signaling pathways involving their reactive oxygen species (ROS)-scavenging activity. These polyphenols may also act as pro-oxidants under certain conditions, especially at high concentrations. Epigenetic modifications, including dysregulation of noncoding RNAs (ncRNAs) such as microRNAs, long noncoding RNAs, and circular RNAs are now known to be involved in the anticancer effects of polyphenols. These polyphenols can modulate the expression/activity of the component molecules in ROS-scavenger-triggered anticancer pathways (RSTAPs) by increasing the expression of tumor-suppressive ncRNAs and decreasing the expression of oncogenic ncRNAs in general. Multiple ncRNAs are similarly modulated by multiple polyphenols. Many of the targets of ncRNAs affected by these polyphenols are components of RSTAPs. Therefore, ncRNA modulation may enhance the anticancer effects of polyphenols via RSTAPs in an additive or synergistic manner, although other mechanisms may be operating as well.
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Affiliation(s)
- Sumio Hayakawa
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan
- Correspondence: (S.H.); (N.M.); Tel.: +81-3-3822-2131 (S.H.); +81-54-264-5531 (N.M.)
| | - Tomokazu Ohishi
- Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Shizuoka 410-0301, Japan
- Institute of Microbial Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation, Shinagawa-ku, Tokyo 141-0021, Japan
| | - Yumiko Oishi
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan
| | - Mamoru Isemura
- Tea Science Center, University of Shizuoka, Shizuoka 422-8526, Japan
| | - Noriyuki Miyoshi
- Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
- Correspondence: (S.H.); (N.M.); Tel.: +81-3-3822-2131 (S.H.); +81-54-264-5531 (N.M.)
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Lo Iacono M, Gaggianesi M, Bianca P, Brancato OR, Muratore G, Modica C, Roozafzay N, Shams K, Colarossi L, Colarossi C, Memeo L, Turdo A, Veschi V, Di Franco S, Todaro M, Stassi G. Destroying the Shield of Cancer Stem Cells: Natural Compounds as Promising Players in Cancer Therapy. J Clin Med 2022; 11:6996. [PMID: 36498571 PMCID: PMC9737492 DOI: 10.3390/jcm11236996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/21/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
In a scenario where eco-sustainability and a reduction in chemotherapeutic drug waste are certainly a prerogative to safeguard the biosphere, the use of natural products (NPs) represents an alternative therapeutic approach to counteract cancer diseases. The presence of a heterogeneous cancer stem cell (CSC) population within a tumor bulk is related to disease recurrence and therapy resistance. For this reason, CSC targeting presents a promising strategy for hampering cancer recurrence. Increasing evidence shows that NPs can inhibit crucial signaling pathways involved in the maintenance of CSC stemness and sensitize CSCs to standard chemotherapeutic treatments. Moreover, their limited toxicity and low costs for large-scale production could accelerate the use of NPs in clinical settings. In this review, we will summarize the most relevant studies regarding the effects of NPs derived from major natural sources, e.g., food, botanical, and marine species, on CSCs, elucidating their use in pre-clinical and clinical studies.
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Affiliation(s)
- Melania Lo Iacono
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Miriam Gaggianesi
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
| | - Paola Bianca
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Ornella Roberta Brancato
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
| | - Giampaolo Muratore
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Chiara Modica
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
| | - Narges Roozafzay
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Kimiya Shams
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Lorenzo Colarossi
- Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, 95029 Catania, Italy
| | - Cristina Colarossi
- Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, 95029 Catania, Italy
| | - Lorenzo Memeo
- Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, 95029 Catania, Italy
| | - Alice Turdo
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Veronica Veschi
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
| | - Simone Di Franco
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
| | - Matilde Todaro
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Giorgio Stassi
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
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Okem A, Henstra C, Lambert M, Hayeshi R. A review of the pharmacodynamic effect of chemo-herbal drug combinations therapy for cancer treatment. MEDICINE IN DRUG DISCOVERY 2022. [DOI: 10.1016/j.medidd.2022.100147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Nisar S, Masoodi T, Prabhu KS, Kuttikrishnan S, Zarif L, Khatoon S, Ali S, Uddin S, Akil AAS, Singh M, Macha MA, Bhat AA. Natural products as chemo-radiation therapy sensitizers in cancers. Biomed Pharmacother 2022; 154:113610. [PMID: 36030591 DOI: 10.1016/j.biopha.2022.113610] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/24/2022] [Accepted: 08/24/2022] [Indexed: 11/02/2022] Open
Abstract
Cancer is a devastating disease and is the second leading cause of death worldwide. Surgery, chemotherapy (CT), and/or radiation therapy (RT) are the treatment of choice for most advanced tumors. Unfortunately, treatment failure due to intrinsic and acquired resistance to the current CT and RT is a significant challenge associated with poor patient prognosis. There is an urgent need to develop and identify agents that can sensitize tumor cells to chemo-radiation therapy (CRT) with minimal cytotoxicity to the healthy tissues. While many recent studies have identified the underlying molecular mechanisms and therapeutic targets for CRT failure, using small molecule inhibitors to chemo/radio sensitize tumors is associated with high toxicity and increased morbidity. Natural products have long been used as chemopreventive agents in many cancers. Combining many of these compounds with the standard chemotherapeutic agents or with RT has shown synergistic effects on cancer cell death and overall improvement in patient survival. Based on the available data, there is strong evidence that natural products have a robust therapeutic potential along with CRT and their well-known chemopreventive effects in many solid tumors. This review article reports updated literature on different natural products used as CT or RT sensitizers in many solid tumors. This is the first review discussing CT and RT sensitizers together in cancer.
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Affiliation(s)
- Sabah Nisar
- Depertment of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Tariq Masoodi
- Laboratory of Cancer immunology and genetics, Sidra Medicine, Qatar
| | - Kirti S Prabhu
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Qatar
| | - Shilpa Kuttikrishnan
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Qatar
| | - Lubna Zarif
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Qatar
| | - Summaiya Khatoon
- Depertment of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Shahid Ali
- International Potato Center (CIP), Shillong, Meghalaya, India
| | - Shahab Uddin
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Qatar; Laboratory Animal Research Center, Qatar University, Doha, Qatar
| | - Ammira Al-Shabeeb Akil
- Depertment of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Mayank Singh
- Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, AIIMS, New Delhi, India.
| | - Muzafar A Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Jammu & Kashmir, India.
| | - Ajaz A Bhat
- Depertment of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar.
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Farhan M. Green Tea Catechins: Nature’s Way of Preventing and Treating Cancer. Int J Mol Sci 2022; 23:ijms231810713. [PMID: 36142616 PMCID: PMC9501439 DOI: 10.3390/ijms231810713] [Citation(s) in RCA: 71] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/12/2022] [Accepted: 09/12/2022] [Indexed: 12/02/2022] Open
Abstract
Green tea’s (Camellia sinensis) anticancer and anti-inflammatory effects are well-known. Catechins are the most effective antioxidants among the physiologically active compounds found in Camellia sinesis. Recent research demonstrates that the number of hydroxyl groups and the presence of specific structural groups have a substantial impact on the antioxidant activity of catechins. Unfermented green tea is the finest source of these chemicals. Catechins have the ability to effectively neutralize reactive oxygen species. The catechin derivatives of green tea include epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG). EGCG has the greatest anti-inflammatory and anticancer potential. Notably, catechins in green tea have been explored for their ability to prevent a variety of cancers. Literature evidence, based on epidemiological and laboratory studies, indicates that green tea catechins have certain properties that can serve as the basis for their consideration as lead molecules in the synthesis of novel anticancer drugs and for further exploration of their role as pharmacologically active natural adjuvants to standard chemotherapeutics. The various sections of the article will focus on how catechins affect the survival, proliferation, invasion, angiogenesis, and metastasis of tumors by modulating cellular pathways.
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Affiliation(s)
- Mohd Farhan
- Department of Basic Sciences, Preparatory Year Deanship, King Faisal University, Al-Ahsa 31982, Saudi Arabia
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Ghosh S, Singh R, Vanwinkle ZM, Guo H, Vemula PK, Goel A, Haribabu B, Jala VR. Microbial metabolite restricts 5-fluorouracil-resistant colonic tumor progression by sensitizing drug transporters via regulation of FOXO3-FOXM1 axis. Theranostics 2022; 12:5574-5595. [PMID: 35910798 PMCID: PMC9330515 DOI: 10.7150/thno.70754] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 07/06/2022] [Indexed: 11/20/2022] Open
Abstract
The survival rate of colorectal cancer patients is adversely affected by the selection of tumors resistant to conventional anti-cancer drugs such as 5-fluorouracil (5FU). Although there is mounting evidence that commensal gut microbiota is essential for effective colon cancer treatment, the detailed molecular mechanisms and the role of gut microbial metabolites remain elusive. The goal of this study is to decipher the impact and mechanisms of gut microbial metabolite, urolithin A (UroA) and its structural analogue, UAS03 on reversal of 5FU-resistant (5FUR) colon cancers. Methods: We have utilized the SW480 and HCT-116 parental (5FU-sensitive) and 5FUR colon cancer cells to examine the chemosensitization effects of UroA or UAS03 by using both in vitro and in vivo models. The effects of mono (UroA/UAS03/5FU) and combinatorial therapy (UroA/UAS03 + 5FU) on cell proliferation, apoptosis, cell migration and invasion, regulation of epithelial mesenchymal transition (EMT) mediators, expression and activities of drug transporters, and their regulatory transcription factors were examined using molecular, cellular, immunological and flowcytometric methods. Further, the anti-tumor effects of mono/combination therapy (UroA or UAS03 or 5FU or UroA/UAS03 + 5FU) were examined using pre-clinical models of 5FUR-tumor xenografts in NRGS mice and azoxymethane (AOM)-dextran sodium sulfate (DSS)-induced colon tumors. Results: Our data showed that UroA or UAS03 in combination with 5FU significantly inhibited cell viability, proliferation, invasiveness as well as induced apoptosis of the 5FUR colon cancer cells compared to mono treatments. Mechanistically, UroA or UAS03 chemosensitized the 5FUR cancer cells by downregulating the expression and activities of drug transporters (MDR1, BCRP, MRP2 and MRP7) leading to a decrease in the efflux of 5FU. Further, our data suggested the UroA or UAS03 chemosensitized 5FUR cancer cells to 5FU treatment through regulating FOXO3-FOXM1 axis. Oral treatment with UroA or UAS03 in combination with low dose i.p. 5FU significantly reduced the growth of 5FUR-tumor xenografts in NRGS mice. Further, combination therapy significantly abrogated colonic tumors in AOM-DSS-induced colon tumors in mice. Conclusions: In summary, gut microbial metabolite UroA and its structural analogue UAS03 chemosensitized the 5FUR colon cancers for effective 5FU chemotherapy. This study provided the novel characteristics of gut microbial metabolites to have significant translational implications in drug-resistant cancer therapeutics.
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Affiliation(s)
- Sweta Ghosh
- Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville, Louisville, KY, USA
| | - Rajbir Singh
- Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville, Louisville, KY, USA
| | - Zachary Matthew Vanwinkle
- Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville, Louisville, KY, USA
| | - Haixun Guo
- Department of Radiology, Center for Predictive Medicine, University of Louisville, Louisville, KY, USA
| | - Praveen Kumar Vemula
- Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka 560065, India
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Bodduluri Haribabu
- Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville, Louisville, KY, USA
| | - Venkatakrishna Rao Jala
- Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville, Louisville, KY, USA
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Zhao L, Zhao H, Zhao Y, Sui M, Liu J, Li P, Liu N, Zhang K. Role of Ginseng, Quercetin, and Tea in Enhancing Chemotherapeutic Efficacy of Colorectal Cancer. Front Med (Lausanne) 2022; 9:939424. [PMID: 35795631 PMCID: PMC9252166 DOI: 10.3389/fmed.2022.939424] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/24/2022] [Indexed: 12/15/2022] Open
Abstract
As the most common gastrointestinal malignancy, colorectal cancer (CRC) remains a leading cause of cancer death worldwide. Although multimodal chemotherapy has effectively improved the prognosis of patients with CRC in recent years, severe chemotherapy-associated side effects and chemoresistance still greatly impair efficacy and limit its clinical application. In response to these challenges, an increasing number of traditional Chinese medicines have been used as synergistic agents for CRC administration. In particular, ginseng, quercetin, and tea, three common dietary supplements, have been shown to possess the potent capacity of enhancing the sensitivity of various chemotherapy drugs and reducing their side effects. Ginseng, also named “the king of herbs”, contains a great variety of anti-cancer compounds, among which ginsenosides are the most abundant and major research objects of various anti-tumor studies. Quercetin is a flavonoid and has been detected in multiple common foods, which possesses a wide range of pharmacological properties, especially with stronger anti-cancer and anti-inflammatory effects. As one of the most consumed beverages, tea has become particularly prevalent in both West and East in recent years. Tea and its major extracts, such as catechins and various constituents, were capable of significantly improving life quality and exerting anti-cancer effects both in vivo and in vitro. In this review, we mainly focused on the adjunctive effects of the three herbs and their constituents on the chemotherapy process of CRC.
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Affiliation(s)
- Linxian Zhao
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Hongyu Zhao
- Gastroenterology and Center of Digestive Endoscopy, The Second Hospital of Jilin University, Changchun, China
| | - Yongqing Zhao
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Mingxiu Sui
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Jinping Liu
- Research Center of Natural Drugs, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Pingya Li
- Research Center of Natural Drugs, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Ning Liu
- Department of Central Laboratory, The Second Hospital of Jilin University, Changchun, China
- *Correspondence: Ning Liu
| | - Kai Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
- Kai Zhang
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Sritharan S, Guha S, Hazarika S, Sivalingam N. Meta analysis of bioactive compounds, miRNA, siRNA and cell death regulators as sensitizers to doxorubicin induced chemoresistance. Apoptosis 2022; 27:622-646. [PMID: 35716277 DOI: 10.1007/s10495-022-01742-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2022] [Indexed: 11/02/2022]
Abstract
Cancer has presented to be the most challenging disease, contributing to one in six mortalities worldwide. The current treatment regimen involves multiple rounds of chemotherapy administration, alone or in combination. The treatment has adverse effects including cardiomyopathy, hepatotoxicity, and nephrotoxicity. In addition, the development of resistance to chemo has been attributed to cancer relapse and low patient overall survivability. Multiple drug resistance development may be through numerous factors such as up-regulation of drug transporters, drug inactivation, alteration of drug targets and drug degradation. Doxorubicin is a widely used first line chemotherapeutic drug for a myriad of cancers. It has multiple intracellular targets, DNA intercalation, adduct formation, topoisomerase inhibition, iron chelation, reactive oxygen species generation and promotes immune mediated clearance of the tumor. Agents that can sensitize the resistant cancer cells to the chemotherapeutic drug are currently the focus to improve the clinical efficiency of cancer therapy. This review summarizes the recent 10-year research on the use of natural phytochemicals, inhibitors of apoptosis and autophagy, miRNAs, siRNAs and nanoformulations being investigated for doxorubicin chemosensitization.
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Affiliation(s)
- Sruthi Sritharan
- Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, Faculty of Engineering and Technology, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, Chengalpattu District, Chennai, Tamil Nadu, 603203, India
| | - Sampurna Guha
- Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, Faculty of Engineering and Technology, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, Chengalpattu District, Chennai, Tamil Nadu, 603203, India
| | - Snoopy Hazarika
- Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, Faculty of Engineering and Technology, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, Chengalpattu District, Chennai, Tamil Nadu, 603203, India
| | - Nageswaran Sivalingam
- Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, Faculty of Engineering and Technology, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, Chengalpattu District, Chennai, Tamil Nadu, 603203, India.
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Anti-Cancer Effects of Dietary Polyphenols via ROS-Mediated Pathway with Their Modulation of MicroRNAs. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27123816. [PMID: 35744941 PMCID: PMC9227902 DOI: 10.3390/molecules27123816] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 06/09/2022] [Accepted: 06/10/2022] [Indexed: 12/23/2022]
Abstract
Consumption of coffee, tea, wine, curry, and soybeans has been linked to a lower risk of cancer in epidemiological studies. Several cell-based and animal studies have shown that dietary polyphenols like chlorogenic acid, curcumin, epigallocatechin-3-O-gallate, genistein, quercetin and resveratrol play a major role in these anticancer effects. Several mechanisms have been proposed to explain the anticancer effects of polyphenols. Depending on the cellular microenvironment, these polyphenols can exert double-faced actions as either an antioxidant or a prooxidant, and one of the representative anticancer mechanisms is a reactive oxygen species (ROS)-mediated mechanism. These polyphenols can also influence microRNA (miR) expression. In general, they can modulate the expression/activity of the constituent molecules in ROS-mediated anticancer pathways by increasing the expression of tumor-suppressive miRs and decreasing the expression of oncogenic miRs. Thus, miR modulation may enhance the anticancer effects of polyphenols through the ROS-mediated pathways in an additive or synergistic manner. More precise human clinical studies on the effects of dietary polyphenols on miR expression will provide convincing evidence of the preventive roles of dietary polyphenols in cancer and other diseases.
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Ng CX, Affendi MM, Chong PP, Lee SH. The Potential of Plant-Derived Extracts and Compounds to Augment Anticancer Effects of Chemotherapeutic Drugs. Nutr Cancer 2022; 74:3058-3076. [PMID: 35675271 DOI: 10.1080/01635581.2022.2069274] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Plant extracts comprise a complex mixture of natural compounds with diverse biological activities including anticancer activities. This has made the use of plant extracts a trending strategy in cancer treatment. In addition, plants' active constituents such as polyphenols could confer protective effects on normal cells against damage by free radicals as well as lessen the toxicity of chemotherapeutic drugs. Recently, many emerging studies revealed the combinatory uses of plant extracts and individual therapeutic compounds that could be a promising panacea in hampering multiple signaling pathways involved in cancer development and progression. Besides enhancing the therapeutic efficacy, this has also been proven to reduce the dosage of chemotherapeutic drugs used, and hence overcome multiple drug resistance and minimize treatment side effects. Notably, combined use of plant extracts with chemotherapeutics drugs was shown to enhance anticancer effects through modulating various signaling pathways, such as P13K/AKT, NF-κB, JNK, ERK, WNT/β-catenin, and many more. Hence, this review aims to comprehensively summarize both In Vitro and In Vivo mechanisms of actions of well-studied plant extracts, such as Ganoderma Lucidum, Korean red ginseng, Garcinia sp., curcumin, and luteolin extracts in augmenting anticancer properties of the conventional chemotherapeutic drugs from an extensive literature search of recent publications.
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Affiliation(s)
- Chu Xin Ng
- School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Selangor, Malaysia
| | - Muzaira Mazrul Affendi
- School of Health Sciences, Faculty of Medicine and Health Sciences, International Medical University, Wilayah Persekutuan Kuala Lumpur, Malaysia
| | - Pei Pei Chong
- School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Selangor, Malaysia
| | - Sau Har Lee
- School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Selangor, Malaysia.,Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor's University, Selangor, Malaysia
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43
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Modulation of Notch Signaling Pathway by Bioactive Dietary Agents. Int J Mol Sci 2022; 23:ijms23073532. [PMID: 35408894 PMCID: PMC8998406 DOI: 10.3390/ijms23073532] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 03/19/2022] [Accepted: 03/22/2022] [Indexed: 12/15/2022] Open
Abstract
Notch signaling is often aberrantly activated in solid and hematological cancers and regulates cell fate decisions and the maintenance of cancer stem cells. In addition, increased expression of Notch pathway components is clinically associated with poorer prognosis in several types of cancer. Targeting Notch may have chemopreventive and anti-cancer effects, leading to reduced disease incidence and improved survival. While therapeutic agents are currently in development to achieve this goal, several researchers have turned their attention to dietary and natural agents for targeting Notch signaling. Given their natural abundance from food sources, the use of diet-derived agents to target Notch signaling offers the potential advantage of low toxicity to normal tissue. In this review, we discuss several dietary agents including curcumin, EGCG, resveratrol, and isothiocyanates, which modulate Notch pathway components in a context-dependent manner. Dietary agents modulate Notch signaling in several types of cancer and concurrently decrease in vitro cell viability and in vivo tumor growth, suggesting a potential role for their clinical use to target Notch pathway components, either alone or in combination with current therapeutic agents.
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44
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Ohishi T, Hayakawa S, Miyoshi N. Involvement of microRNA modifications in anticancer effects of major polyphenols from green tea, coffee, wine, and curry. Crit Rev Food Sci Nutr 2022; 63:7148-7179. [PMID: 35289676 DOI: 10.1080/10408398.2022.2038540] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Epidemiological studies have shown that consumption of green tea, coffee, wine, and curry may contribute to a reduced risk of various cancers. However, there are some cancer site-specific differences in their effects; for example, the consumption of tea or wine may reduce bladder cancer risk, whereas coffee consumption may increase the risk. Animal and cell-based experiments have been used to elucidate the anticancer mechanisms of these compounds, with reactive oxygen species (ROS)-based mechanisms emerging as likely candidates. Chlorogenic acid (CGA), curcumin (CUR), epigallocatechin gallate (EGCG), and resveratrol (RSV) can act as antioxidants that activate AMP-activated protein kinase (AMPK) to downregulate ROS, and as prooxidants to generate ROS, leading to the downregulation of NF-κB. Polyphenols can modulate miRNA (miR) expression, with these dietary polyphenols shown to downregulate tumor-promoting miR-21. CUR, EGCG, and RSV can upregulate tumor-suppressing miR-16, 34a, 145, and 200c, but downregulate tumor-promoting miR-25a. CGA, EGCG, and RSV downregulate tumor-suppressing miR-20a, 93, and 106b. The effects of miRs may combine with ROS-mediated pathways, enhancing the anticancer effects of these polyphenols. More precise analysis is needed to determine how the different modulations of miRs by polyphenols relate to the cancer site-specific differences found in epidemiological studies related to the consumption of foods containing these polyphenols.
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Affiliation(s)
- Tomokazu Ohishi
- Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Shizuoka, Japan
| | - Sumio Hayakawa
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Noriyuki Miyoshi
- Laboratory of Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan
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45
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Moracci L, Sensi F, Biccari A, Crotti S, Gaio E, Benetti F, Traldi P, Pucciarelli S, Agostini M. An investigation on [5 fluorouracil and epigallocatechin-3-gallate] complex activity on HT-29 cell death and its stability in gastrointestinal fluid. Oncotarget 2022; 13:476-489. [PMID: 35251495 PMCID: PMC8893781 DOI: 10.18632/oncotarget.28207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 02/17/2022] [Indexed: 12/24/2022] Open
Abstract
Recently an enhancement of the sensitivity of colorectal cancer (CRC) cells by 5-fluorouracil (5FU) due to the concurrent treatment with epigallocatechin-3-gallate (EGCG) has been found. In the present paper, to investigate on this aspect, adenocarcinoma cells HT29 were treated with 5FU, EGCG and an equimolar mixture of 5FU and EGCG ([5FU+EGCG]) and cell viability was determined. While 5FU exhibits a clear activity, EGCG alone does not express any activity. However by treating the cells with [5FU+EGCG] a strong effect of EGCG is evidenced: the sensitivity of HT29 cells to 5FU was increased by 12-fold. A simulation of the behavior of [5FU+EGCG] in different compartments of the gastrointestinal digestion model was also performed. 5FU and EGCG solubilized into a mixture of digestive fluids analyzed by mass spectrometry did not lead to signals of 5FU, EGCG and the related complex, while by diluting the solution they become detectable. On the contrary, when 5FU and EGCG are submitted to the step-by-step digestion model procedure, the analysis did not show the presence of 5FU, EGCG and [5FU+EGCG]. This behaviour could be ascribed to the instability of these compounds due to the too severe digestion conditions and/or to the complexity of the matrix which could lead in ESI conditions to the suppression of the signals of the analytes of interest.
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Affiliation(s)
- Laura Moracci
- Nano-Inspired Biomedicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.,General Surgical Clinic 3, Department of Surgical, Oncological and Gastroentrological Sciences, University of Padua, Padova, Italy
| | - Francesca Sensi
- Nano-Inspired Biomedicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.,Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, Mestre, Venice, Italy
| | - Andrea Biccari
- Nano-Inspired Biomedicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.,General Surgical Clinic 3, Department of Surgical, Oncological and Gastroentrological Sciences, University of Padua, Padova, Italy
| | - Sara Crotti
- Nano-Inspired Biomedicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.,General Surgical Clinic 3, Department of Surgical, Oncological and Gastroentrological Sciences, University of Padua, Padova, Italy
| | - Elisa Gaio
- ECSIN-European Center for the Sustainable Impact of Nanotechnology, ECAMRICERT SRL, Padova, Italy
| | - Federico Benetti
- ECSIN-European Center for the Sustainable Impact of Nanotechnology, ECAMRICERT SRL, Padova, Italy
| | - Pietro Traldi
- Nano-Inspired Biomedicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy
| | - Salvatore Pucciarelli
- Nano-Inspired Biomedicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.,General Surgical Clinic 3, Department of Surgical, Oncological and Gastroentrological Sciences, University of Padua, Padova, Italy
| | - Marco Agostini
- Nano-Inspired Biomedicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.,General Surgical Clinic 3, Department of Surgical, Oncological and Gastroentrological Sciences, University of Padua, Padova, Italy
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46
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Kansal V, Agarwal A, Harbour A, Farooqi H, Singh VK, Prasad R. Regular Intake of Green Tea Polyphenols Suppresses the Development of Nonmelanoma Skin Cancer through miR-29-Mediated Epigenetic Modifications. J Clin Med 2022; 11:jcm11020398. [PMID: 35054091 PMCID: PMC8777720 DOI: 10.3390/jcm11020398] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 12/26/2021] [Accepted: 01/10/2022] [Indexed: 12/11/2022] Open
Abstract
Previously, we and others have shown that the regular intake of green tea polyphenols (GTPs) reduces ultraviolet B (UVB) radiation-induced skin cancer by targeting multiple signaling pathways, including DNA damage, DNA repair, immunosuppression, and inflammation. Here, we determine the effect of GTPs on UVB-induced epigenetic changes, emphasizing DNA hypermethylation in UV-exposed skin and tumors and their association with miR-29, a key regulator of DNA methyltransferases (DNMTs). Skin cancer was induced in SKH-1 hairless mice following repeated exposures of UVB radiation (180 mJ/cm2, three times/week, 24 weeks) with or without GTPs supplementation (0.2%) in drinking water. Regular intake of GTPs inhibited tumor growth by hindering the cascade of DNA hypermethylation events. GTPs supplementation significantly blocked UVB-induced DNA hypermethylation in the skin (up to 35%; p < 0.0001) and in tumors (up to 50%; p < 0.0001). Experimental results showed that the levels of DNA hypermethylation were higher in GTPs-treated mice than in the control group. The expressions of miR-29a, miR-29b, and miR-29c were markedly decreased in UV-induced skin tumors, and GTPs administration blocked UVB-induced miR-29s depletion. Furthermore, these observations were verified using the in vitro approach in human skin cancer cells (A431) followed by treatment with GTPs or mimics of miR-29c. Increased levels of miR-29 were observed in GTPs-treated A431 cells, resulting in increased TET activity and decreased DNA hypermethylation. In conclusion, UVB-mediated miR-29 depletion promotes DNA hypermethylation and leads to enhanced tumor growth by silencing tumor suppressors. Regular intake of GTPs rescued UVB-induced miR-29 depletion and prevented tumor growth by maintaining reduced DNA hypermethylation and activating tumor suppressors. Our observations suggest that miR-based strategies and regular consumption of GTPs could minimize the risk of UVB-induced skin cancers and contribute to better management of NMSCs.
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Affiliation(s)
- Vikash Kansal
- Department of Otolaryngology, Emory University, Atlanta, GA 30322, USA;
| | - Anshu Agarwal
- Department of Zoology, Agra College, Agra 282001, India;
- Department of Biotechnology, Hamdard University, New Delhi 110048, India
| | - Angela Harbour
- College of Medicine, Florida State University, Tallahassee, FL 32304, USA;
| | - Humaira Farooqi
- Department of Biotechnology, Hamdard University, New Delhi 110048, India
- Correspondence: (H.F.); (V.K.S.); (R.P.)
| | - Vijay Kumar Singh
- Department of Zoology, Agra College, Agra 282001, India;
- Correspondence: (H.F.); (V.K.S.); (R.P.)
| | - Ram Prasad
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Correspondence: (H.F.); (V.K.S.); (R.P.)
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Maleki Dana P, Sadoughi F, Asemi Z, Yousefi B. The role of polyphenols in overcoming cancer drug resistance: a comprehensive review. Cell Mol Biol Lett 2022; 27:1. [PMID: 34979906 PMCID: PMC8903685 DOI: 10.1186/s11658-021-00301-9] [Citation(s) in RCA: 118] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 12/17/2021] [Indexed: 12/13/2022] Open
Abstract
Chemotherapeutic drugs are used to treat advanced stages of cancer or following surgery. However, cancers often develop resistance against drugs, leading to failure of treatment and recurrence of the disease. Polyphenols are a family of organic compounds with more than 10,000 members which have a three-membered flavan ring system in common. These natural compounds are known for their beneficial properties, such as free radical scavenging, decreasing oxidative stress, and modulating inflammation. Herein, we discuss the role of polyphenols (mainly curcumin, resveratrol, and epigallocatechin gallate [EGCG]) in different aspects of cancer drug resistance. Increasing drug uptake by tumor cells, decreasing drug metabolism by enzymes (e.g. cytochromes and glutathione-S-transferases), and reducing drug efflux are some of the mechanisms by which polyphenols increase the sensitivity of cancer cells to chemotherapeutic agents. Polyphenols also affect other targets for overcoming chemoresistance in cancer cells, including cell death (i.e. autophagy and apoptosis), EMT, ROS, DNA repair processes, cancer stem cells, and epigenetics (e.g. miRNAs).
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Affiliation(s)
- Parisa Maleki Dana
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Fatemeh Sadoughi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran.
| | - Bahman Yousefi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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48
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Emerging Therapeutic Agents for Colorectal Cancer. Molecules 2021; 26:molecules26247463. [PMID: 34946546 PMCID: PMC8707340 DOI: 10.3390/molecules26247463] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/03/2021] [Accepted: 12/06/2021] [Indexed: 02/07/2023] Open
Abstract
There are promising new therapeutic agents for CRC patients, including novel small-molecule inhibitors and immune checkpoint blockers. We focused on emerging CRC’s therapeutic agents that have shown the potential for progress in clinical practice. This review provides an overview of tyrosine kinase inhibitors targeting VEGF and KIT, BRAF and MEK inhibitors, TLR9 agonist, STAT3 inhibitors, and immune checkpoint blockers (PD1/PDL-1 inhibitors), for which recent advances have been reported. These new agents have the potential to provide benefits to CRC patients with unmet medical needs.
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49
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Hu Z, Li M, Cao Y, Akan OD, Guo T, Luo F. Targeting AMPK Signaling by Dietary Polyphenols in Cancer Prevention. Mol Nutr Food Res 2021; 66:e2100732. [PMID: 34802178 DOI: 10.1002/mnfr.202100732] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 11/03/2021] [Indexed: 12/14/2022]
Abstract
Cancer is a serious public health problem in the world and a major disease affecting human health. Dietary polyphenols have shown good potential in the treatment of various cancers. It is worth noting that cancer cells usually exhibit metabolic abnormalities of high glucose intake and inefficient utilization. AMPK is the key molecule in the regulation of energy metabolism and is closely related with obesity and diabetes. Recent studies indicate that AMPK also plays an important role in cancer prevention and regulating cancer-related genes and pathways, and dietary polyphenols can significantly regulate AMPK activity. In this review, the progress of dietary polyphenols preventing carcinogenesis via AMPK pathway is systemically summarized. From the viewpoint of interfering energy metabolism, the anti-cancer effects of dietary polyphenols are explained. AMPK pathway modulated by different dietary polyphenols affects pathways and target genes are summarized. Dietary polyphenols exert anti-cancer effect through the target molecules regulated by AMPK, which broadens the understanding of polyphenols anti-cancer mechanisms and provides value reference for the investigators of the novel field.
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Affiliation(s)
- Zuomin Hu
- Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Deeply Processing and Quality Control of Cereals and Oils, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha, Hunan, 410004, China
| | - Mengyuan Li
- Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Deeply Processing and Quality Control of Cereals and Oils, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha, Hunan, 410004, China
| | - Yunyun Cao
- Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Deeply Processing and Quality Control of Cereals and Oils, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha, Hunan, 410004, China
| | - Otobong Donald Akan
- Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Deeply Processing and Quality Control of Cereals and Oils, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha, Hunan, 410004, China
| | - Tianyi Guo
- Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Deeply Processing and Quality Control of Cereals and Oils, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha, Hunan, 410004, China
| | - Feijun Luo
- Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Deeply Processing and Quality Control of Cereals and Oils, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changsha, Hunan, 410004, China
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50
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Silva VR, Santos LDS, Dias RB, Quadros CA, Bezerra DP. Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells. Cancer Commun (Lond) 2021; 41:1275-1313. [PMID: 34791817 PMCID: PMC8696218 DOI: 10.1002/cac2.12235] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/28/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, including the Wingless (Wnt)/β-catenin, Notch, Hedgehog, nuclear factor kappa B (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), peroxisome proliferator-activated receptor (PPAR), phosphatidyl-inositol-3-kinase/Akt/mechanistic target of rapamycin (PI3K/Akt/mTOR), and transforming growth factor-β (TGF-β)/Smad pathways. In this review, we summarize the strategies for eradicating CRC stem cells by modulating these dysregulated pathways, which will contribute to the study of potential therapeutic schemes, combining conventional drugs with CSC-targeting drugs, and allowing better cure rates in anti-CRC therapy.
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Affiliation(s)
- Valdenizia R Silva
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil
| | - Luciano de S Santos
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil
| | - Rosane B Dias
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil
| | - Claudio A Quadros
- São Rafael Hospital, Rede D'Or/São Luiz, Salvador, Bahia, 41253-190, Brazil.,Bahia State University, Salvador, Bahia, 41150-000, Brazil
| | - Daniel P Bezerra
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil
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