Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis
Wheaton, William W; Weinberg, Samuel E; Hamanaka, Robert B; Soberanes, Saul; Sullivan, Lucas B; Anso, Elena; Glasauer, Andrea; Dufour, Eric; Mutlu, Gokhan; Budinger, Scott G R; Chandel, Navdeep S (2014)
Wheaton, William W
Weinberg, Samuel E
Hamanaka, Robert B
Soberanes, Saul
Sullivan, Lucas B
Anso, Elena
Glasauer, Andrea
Dufour, Eric
Mutlu, Gokhan
Budinger, Scott G R
Chandel, Navdeep S
2014
eLife 3
e02242
BioMediTech - BioMediTech
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:uta-201609292369
https://urn.fi/URN:NBN:fi:uta-201609292369
Tiivistelmä
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.
Kokoelmat
- Artikkelit [6140]