Regulation of Proliferation and Autophagy and Its Possible Mechanisms of Resveratrol on HepG2 Cells in Hypoxia

Abstract

Resveratrol as a polyphenolic compound is naturally enriched in grapes, red wine and peanuts. Resveratrol has been reported to have potent anticancer and antioxidant properties. Most studies about the anti-cancer effect of resveratrol have been described previously when cells on the normoxia. The effect of resveratrol in hypoxia, the environment which mimics the state of tumor in vivo remains unclear. In this study, human hepatocellular carcinoma HepG2 cells were used to understand the effects and the possible mechanisms by which resveratrol acts as an anticancer agent in hypoxic conditions (1% O2). Our data show that resveratrol significantly inhibits HepG2 cell viability in hypoxia, and promotes hypoxia stress induced autophagy as well. We also found that the NAD-dependent deacetylase (Sirt1) and sphingosine kinase 1 (SPK1) might be involved in the effects of resveratrol in hypoxia. Collectively, our studies reveal the possible mechanisms of insensitive effect of the resveratrol in hypoxia, and further clarify the anticancer effect of resveratrol on solid tumor cells, providing a reference for drug development of resveratrol.