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.

Resveratrol modulates epigenetic regulators of promoter histone methylation and acetylation that restores BRCA1, p53, p21CIP1 in human breast cancer cell lines

“…To study more closely, we have chosen two breast cancer cell lines-MCF-7 (ER-positive) and MDA-MB-231 triple negative (ER, PR, and HER2 negative) which represents most common type breast cancers in human. In line with previous reports, [26][27][28] we observed a similar growth inhibitory effect of RVT as it decreased the viability of both MCF-7 and MDA-MB-231 cells by 48 hr (Supplementary Information Figure S1). In correlation to the previous reports, 20,29 RVT exposure increased the endogenous level of BRCA1, p53, as well as p21 transcript and protein in a concentration and exposure timedependent manner.…”

Sodium butyrate inhibits migration and induces AMPK‐mTOR pathway‐dependent autophagy and ROS‐mediated apoptosis via the miR‐139‐5p/Bmi‐1 axis in human bladder cancer cells

“…Meanwhile, autophagy induced by NaB was repressed by NAC (Figure I). To explain this effect of ROS on autophagy, we search numerous literatures and find some studies have demonstrate that several anticancer agents including resveratrol or cucurbitacin trigger autophagy through ROS production. One of the underlying mechanisms is that ROS oxidize Atg4 leading to the promoted autophagosome formation .…”

Resveratrol protects podocytes against apoptosis via stimulation of autophagy in a mouse model of diabetic nephropathy

“…Extensive studies have indicated that it plays important podocyte-protective roles in multiple kidney diseases, including DN. Compelling evidence has shown that resveratrol is capable of inducing autophagy in different cancer cell lines202122; however, nothing is known about its effect on autophagy induction in renal cells. In this study, we demonstrated that resveratrol effectively attenuates HG-induced apoptosis of podocytes via the activation of autophagy in db/db mice.…”