Metformin inhibits cancer cell proliferation and epidemiology studies suggest an association with increased survival in cancer patients 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 while 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.
Written by:
Fendt SM, Bell EL, Keibler MA, Davidson SM, Wirth GJ, Fiske B, Mayers JR, Schwab M, Bellinger G, Csibi A, Patnaik A, Blouin MJ, Cantley LC, Guarente LP, Blenis J, Pollak MN, Olumi AF, Vander Heiden M, Stephanopoulos G. Are you the author?
Department of Chemical Engineering, Massachusetts Institute of Technology.
Reference: Cancer Res. 2013 May 17. Epub ahead of print.
doi: 10.1158/0008-5472.CAN-13-0080
PubMed Abstract
PMID: 23687346
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