title: Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells.
abstract: Resveratrol (trans-3,4,5'-trihydroxystilbene) is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3) was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS) generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, Jinan Central Hospital, Affiliated with Shandong University, Jinan, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Lang
authors.affiliation: Department of General Surgery, Rizhao People's Hospital, Rizhao, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Health, Jinan Central Hospital, Affiliated with Shandong University, Jinan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Central Laboratory, Jinan Central Hospital, Affiliated with Shandong University, Jinan, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Jinan Central Hospital, Affiliated with Shandong University, Jinan, China.
authors.forename: Zhenghui
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Cardiology, Qianfoshan Hospital, Affiliated with Shandong University, Jinan, China.
authors.forename: Enkui
authors.initials: E
authors.lastname: Hao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000633:toxicity; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000633:toxicity*
chemical_list: C502778:ATG5 protein, human; D000972:Antineoplastic Agents, Phytogenic; D000071187:Autophagy-Related Protein 5; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013267:Stilbenes; D002738:Chloroquine; D053148:Caspase 3; D000077185:Resveratrol