title: Myricetin inhibits proliferation of cisplatin-resistant cancer cells through a p53-dependent apoptotic pathway.
abstract: Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatin-resistant cancer cell lines, but did not induce apoptosis in the normal ovarian cell line. It induced both Bcl-2 family-dependent intrinsic and DR5 dependent extrinsic apoptosis in OVCAR-3 cells. P53, a multifunctional tumor suppressor, regulated apoptosis in OVCAR-3 cells through a Bcl-2 family protein-dependent pathway. Myricetin did not induce cell cycle arrest in either ovarian cancer cell line. Because of its potency and selectivity against cisplatin-resistant cancer cells, myricetin could potentially be used to overcome cancer chemoresistance against platinum-based therapy.
authors: College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA.
authors: Haizhi
authors: H
authors: Huang
authors: Department of Pharmaceutical Science, West Virginia University, Morgantown, WV 26506, USA.
authors: Allen Y
authors: AY
authors: Chen
authors: College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang University, Hangzhou, Zhejiang 310027, P.R. China.
authors: Xingqian
authors: X
authors: Ye
authors: Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
authors: Bingyun
authors: B
authors: Li
authors: Department of Pharmaceutical Science, West Virginia University, Morgantown, WV 26506, USA.
authors: Yon
authors: Y
authors: Rojanasakul
authors: Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA.
authors: Gary O
authors: GO
authors: Rankin
authors: College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA.
authors: Yi Charlie
authors: YC
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D034741:RNA, Small Interfering; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C040015:myricetin; D002945:Cisplatin