二甲双胍降低癌症发病率秘密被揭开

Metformin reduces endogenous reactive oxygen species and associated DNA damage

Carolyn Algire1, Olga Moiseeva2, Xavier Deschenes-Simard2, Lilian Amrein3, Luca A Petruccelli4, Elena Birman5, Benoit Viollet6, Gerardo Ferbeyre7, and Michael N Pollak8,*

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), and related DNA damage and mutations, but has no effect on similar changes induced by H202, indicating a reduction in endogenous ROS production. Importantly, 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 reported to be associated with exposure to this drug.