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

Overview

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.

publication date

  • May 17, 2013

Research

keywords

  • Glucose
  • Glutamine
  • Metformin
  • Prostatic Neoplasms

Identity

PubMed Central ID

  • PMC3930683

Scopus Document Identifier

  • 84880876347

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-13-0080

PubMed ID

  • 23687346

Additional Document Info

volume

  • 73

issue

  • 14