1. Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism
- Author
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Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Fendt, Sarah-Maria, Bell, Eric L., Keibler, Mark Andrew, Davidson, Shawn Michael, Fiske, Brian Prescott, Mayers, Jared R., Guarente, Leonard Pershing, Vander Heiden, Matthew G., Stephanopoulos, Gregory, Wirth, Gregory J., Schwab, Matthias, Bellinger, Gary, Csibi, Alfred, Patnaik, Akash, Blouin, Marie Jose, Cantley, Lewis C., Blenis, John, Pollak, Michael N., Olumi, Aria F., Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Fendt, Sarah-Maria, Bell, Eric L., Keibler, Mark Andrew, Davidson, Shawn Michael, Fiske, Brian Prescott, Mayers, Jared R., Guarente, Leonard Pershing, Vander Heiden, Matthew G., Stephanopoulos, Gregory, Wirth, Gregory J., Schwab, Matthias, Bellinger, Gary, Csibi, Alfred, Patnaik, Akash, Blouin, Marie Jose, Cantley, Lewis C., Blenis, John, Pollak, Michael N., and Olumi, Aria F.
- Abstract
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., German Science Foundation (Grant FE1185), National Institutes of Health (U.S.), Glenn Foundation for Medical Research, National Institutes of Health (U.S.) (Grant 5-P50-090381-09), National Institutes of Health (U.S.) (Grant 5-P30-CA14051-39), Burroughs Wellcome Fund, Smith Family Foundation, Damon Runyon Cancer Research Foundation, National Institutes of Health (U.S.) (Grant 1R01DK075850-01), National Institutes of Health (U.S.) (Grant 1R01CA160458-01A1)
- Published
- 2014