title: 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.
authors.affiliation: Department of Environmental Health, School of Public Health, Sichuan University, Chengdu 610041, China.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Chen
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: ZunZhen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000037:antagonists & inhibitors* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019457:Chromosome Breakage / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D009153:Mutagens / Q000737:chemistry* / Q000633:toxicity; D014411:Neoplastic Stem Cells / Q000187:drug effects; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D000077185:Resveratrol; D017670:Sodium Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D018053:Arsenites; D009153:Mutagens; D017670:Sodium Compounds; D013267:Stilbenes; C017947:sodium arsenite; D005978:Glutathione; D000077185:Resveratrol
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