Dual role of resveratrol in modulation of genotoxicity induced by sodium arsenite via oxidative stress and apoptosis

Abstract

The potential benefits of resveratrol as an anticancer (proapoptosis) and antioxidant (pro-survival) compound have been studied extensively. However, the role of resveratrol in modulation of the toxicity induced by sodium arsenite (NaAsO₂) is still unclear. In the present study, we examined the effects of resveratrol on NaAsO₂-induced cytotoxicity, DNA and chromosomal damage, cell cycle progression, apoptosis and oxidative stress in human lung adenocarcinoma epithelial (A549) cell line at concentrations from 1 to 20 μM after 24h exposure. Our results revealed that at 1 and 5 μM, resveratrol was found to exert benefit effects, promoting cell viability and proliferation over 24h NaAsO₂ exposure, whereas, resveratrol was showed to inhibit cell survival under the same condition at 20 μM. Corresponding to the opposing effect of resveratrol at low vs. high concentrations, DNA and chromosomal damage, cell apoptotic rate and level of oxidative stress were also alleviated by lower concentrations (1, 5 μM) of resveratrol, but exacerbated by higher concentration (20 μM) resveratrol. Our study implicates that resveratrol is the most beneficial to cells at 1 and 5 μM and caution should be taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical supplement due to its concentration dependent effect.

Keywords: 3-(45-dimethyl thiazol-2-yl)-25-diphenyl tetrazolium bromide; 5,5′-dithiobis-(2-nitrobenzoic acid); AOD; Apoptosis; DMEM; DMSO; DTNB; Dual role; Dulbecco’s modified Eagle’s medium; FBS; GSH; Genotoxcity; MTT; NaAsO(2); OTM; Oxidative stress; PBS; PI; RNase A; ROS; Resveratrol; Ribonuclease A; SOD; Sodium arsenite; average optical density; dimethylsulfoxide; fetal bovine serum; glutathione; olive tail moment; phosphate buffered saline; propidium iodide; reactive oxygen species; sodium arsenite; superoxide dismutase.