Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism
Author(s)Fendt, Sarah-Maria; Bell, Eric L.; Keibler, Mark Andrew; Davidson, Shawn Michael; Wirth, Gregory J.; Fiske, Brian Prescott; Mayers, Jared R.; Schwab, Matthias; Bellinger, Gary; Csibi, Alfred; Patnaik, Akash; Blouin, Marie Jose; Cantley, Lewis C.; Guarente, Leonard Pershing; Blenis, John; Pollak, Michael N.; Olumi, Aria F.; Vander Heiden, Matthew G.; Stephanopoulos, Gregory; ... Show more Show less
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Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemical Engineering
American Association for Cancer Research
Fendt, S.-M., E. L. Bell, M. A. Keibler, S. M. Davidson, G. J. Wirth, B. Fiske, J. R. Mayers, et al. “Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism.” Cancer Research 73, no. 14 (May 17, 2013): 4429–4438.
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