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Cancer Res. 2013 Jul 15;73(14):4429-38. doi: 10.1158/0008-5472.CAN-13-0080. Epub 2013 May 17.

Metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism.

Author information

1
Departments of Chemical Engineering and Biology, Massachusetts Institute of Technology, Cambridge, MA02139, USA.

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.

PMID:
23687346
PMCID:
PMC3930683
DOI:
10.1158/0008-5472.CAN-13-0080
[Indexed for MEDLINE]
Free PMC Article

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