Abstract:
: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 metformin-resistant Saccharomyces cerevisiae NADH dehydrogenase NDI1 was overexpressed. In vivo, the administration of metformin to mice inhibited the growth of control human cancer cells but not those expressing NDI1. Thus, we have demonstrated that metformin's inhibitory effects on cancer progression are cancer cell autonomous and depend on its ability to inhibit mitochondrial complex I.DOI: http://dx.doi.org/10.7554/eLife.02242.001.
journal_name
Elifejournal_title
eLifeauthors
Wheaton WW,Weinberg SE,Hamanaka RB,Soberanes S,Sullivan LB,Anso E,Glasauer A,Dufour E,Mutlu GM,Budigner GS,Chandel NSdoi
10.7554/eLife.02242subject
Has Abstractpub_date
2014-05-13 00:00:00pages
e02242issn
2050-084Xjournal_volume
3pub_type
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