Myricetin inhibits proliferation of cisplatin-resistant cancer cells through a p53-dependent apoptotic pathway

Huang,Haizhi; Chen,Allen  Y.; Ye,Xingqian; Li,Bingyun; Rojanasakul,Yon; Rankin,Gary  O.; Chen,Yi  Charlie

doi:10.3892/ijo.2015.3133

Myricetin inhibits proliferation of cisplatin-resistant cancer cells through a p53-dependent apoptotic pathway

Authors:
- Haizhi Huang
- Allen Y. Chen
- Xingqian Ye
- Bingyun Li
- Yon Rojanasakul
- Gary O. Rankin
- Yi Charlie Chen
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Affiliations: College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA, Department of Pharmaceutical Science, West Virginia University, Morgantown, WV 26506, USA, College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang University, Hangzhou, Zhejiang 310027, P.R. China, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506, USA, Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA
Published online on: August 25, 2015 https://doi.org/10.3892/ijo.2015.3133
Pages: 1494-1502

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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.

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