Abstract LB-169: Metformin reduces somatic cell mutation rate by inhibiting mitochondrial ROS production: relevance to cancer prevention

Abstract

Abstract Pharmacoepidemiological studies provide evidence that use of metformin, a drug commonly prescribed for type II diabetes, is associated with a substantial reduction in cancer risk. Experimental models show that metformin inhibits the growth of certain neoplasms by cell autonomous mechanisms such as activation of AMP kinase with secondary inhibition of protein synthesis, or by an indirect mechanism involving reduction in gluconeogenesis leading to a decline in insulin levels and reduced proliferation of insulin-responsive cancers. Here we show that metformin attenuates paraquat-induced elevations in reactive oxygen species (ROS), DNA damage and mutations, but has no effect on similar changes induced by H202, indicating a reduction in endogenous ROS production. Metformin also inhibited Ras-induced ROS production and DNA damage. Our results reveal previously unrecognized inhibitory effects of metformin on ROS production and somatic cell mutation, providing a novel mechanism for the reduction in cancer risk associated with exposure to this drug. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-169. doi:1538-7445.AM2012-LB-169