Metformin Reduces Endogenous Reactive Oxygen Species and Associated DNA Damage
| Autor: | Michael Pollak, Carolyn Algire, Olga Moiseeva, Elena Birman, Luca A. Petruccelli, Gerardo Ferbeyre, Benoit Viollet, Lilian Amrein, Xavier Deschênes-Simard |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty DNA damage medicine.medical_treatment Enzyme-Linked Immunosorbent Assay Endogeny Biology Pharmacology medicine.disease_cause Cell Line Mice Internal medicine medicine Animals Humans Hypoglycemic Agents Insulin chemistry.chemical_classification Reactive oxygen species Mutation Epidermal Growth Factor Adenylate Kinase Mutagenesis Hydrogen Peroxide Fibroblasts Flow Cytometry Metformin Mice Inbred C57BL Endocrinology Diabetes Mellitus Type 2 Microscopy Fluorescence Oncology chemistry Gluconeogenesis Reactive Oxygen Species NADP DNA Damage medicine.drug |
| Zdroj: | Cancer Prevention Research. 5:536-543 |
| ISSN: | 1940-6215 1940-6207 |
| Popis: | Pharmacoepidemiologic 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. Cancer Prev Res; 5(4); 536–43. ©2012 AACR. |
| Databáze: | OpenAIRE |
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