Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis

Recent epidemiological and laboratory-based studies suggest that the anti-diabetic drug metformin prevents cancer progression. How metformin diminishes tumor growth is not fully understood. In this study, we report that in human cancer cells, metformin inhibits mitochondrial complex I (NADH dehydrogenase) activity and cellular respiration. Metformin inhibited cellular proliferation in the presence of glucose, but induced cell death upon glucose deprivation, indicating that cancer cells rely exclusively on glycolysis for survival in the presence of metformin. Metformin also reduced hypoxic activation of hypoxia-inducible factor 1 (HIF-1). All of these effects of metformin were reversed when the…

• NS
  National Science Council
• NI
  National Institutes of Health

  Awards: 5P01HL071643, T32GM08061, RO1 CA123067, T32 GM08061, T32HL076139, ES015024