stilbenes and sodium-arsenite

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.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Arsenites; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chromosome Breakage; Comet Assay; DNA Damage; Glutathione; Humans; Lung Neoplasms; Micronuclei, Chromosome-Defective; Mutagens; Neoplastic Stem Cells; Osmolar Concentration; Oxidation-Reduction; Oxidative Stress; Resveratrol; Sodium Compounds; Stilbenes

Sodium arsenite (NaAsO2) is a well-established environmental carcinogen that has been found to cause various human malignant tumors. Thus, how to prevent the deleterious effects caused by NaAsO2 has received widely concerns. Resveratrol (3,4',5-trihydroxystilbene), a polyphenol found in numerous plant species, has recently been known as a natural and powerful antioxidant. However, whether resveratrol could attenuate the toxicity of NaAsO2 and its detailed mechanisms have not been reported. In this study, the protective effects of resveratrol against NaAsO2-induced oxidative and genetic damage as well as apoptosis were evaluated for the first time. We demonstrated that cotreatment of human bronchial epithelial cell with 5 μM resveratrol for 24 h effectively reduced the levels of 30 μM NaAsO2-induced reactive oxygen species, chromosomal and DNA damage, and cell apoptosis. Revseratrol was also showed to significantly elevate the concentration of glutathione (GSH) and the activities of its relevant enzymes as compared with NaAsO2 alone, indicating that resveratrol ameliorates the toxicity of NaAsO2 by modulating the process of GSH biosynthesis, recycling and utilization. Our findings further suggest that GSH homeostasis represents one of the detoxification mechanisms responding to NaAsO2 exposure, and resveratrol plays a protective role in the regulation of oxidative and genetic damage as well as apoptosis through the modulation of GSH homeostasis.

Topics: Antioxidants; Apoptosis; Arsenites; Blotting, Western; Bronchi; Cell Line; Cell Survival; DNA Damage; Epithelial Cells; Glutamate-Cysteine Ligase; Glutathione; Glutathione Disulfide; Glutathione Peroxidase; Glutathione Reductase; Homeostasis; Humans; Intracellular Space; Oxidative Stress; Protein Subunits; Reactive Oxygen Species; Resveratrol; Sodium Compounds; Stilbenes