Abstract 2498: Resveratrol administration increases SOD2 and reduces oxidative stress to DNA

Abstract

Abstract Mitochondrial manganese superoxide dismutase (SOD2) activation is a downstream product after stimulation via a variety of signaling pathways from a diversity stimulating agents. Thiols including amifostine (S-2-[3-aminopropylamino]ethylphosphorothioic acid) mesna (sodium-2-mercaptoethanesulfonate), NAC (N-acetyl-L-cysteine) and captopril ([S]-1-[3-mercapto-2-methyl-1-oxo-propyl]-L-proline), are effective inducers of SOD2. Non-thiols including estrogen, cerium oxide, low doses of x-rays, and resveratrol (3,4’,5-trihydroxystilbene) have been shown to induce SOD2 under specific treatment conditions. Studies with resveratrol typically involve continuous exposure of cells for several days before determining the effectiveness of the agent as a radioprotector. In studies reported here, SA-NH murine sarcoma tumor cells established for growth in culture were exposed to a single dose of 50μM resveratrol and analyzed for SOD2 activity from 2hr to 28hr post exposure. Early indications suggest that cells induce SOD2 earlier than typically seen for thiols and other oxidative stress modifiers. Resveratrol increases levels of SOD2 by a factor of 3 compared to controls which is similar to levels observed with thiol exposure. While thiols induce SOD2 via the NFκB pathway, resveratrol acts through the FOXO3a pathway. Studies continue to examine SOD2 activity after exposure to acute exposures resveratrol, amifostine, and x-rays. This work was supported by DOE grant DE-SC0001271 (D.J.G.) and NIH grant RO1-CA132998 (D.J.G.). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2498. doi:10.1158/1538-7445.AM2011-2498