Title: Metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism
Authors: Fendt, Sarah-Maria
Bell, Eric L
Keibler, Mark A
Davidson, Shawn M
Wirth, Gregory J
Fiske, Brian
Mayers, Jared R
Schwab, Matthias
Bellinger, Gary
Csibi, Alfredo
Patnaik, Akash
Blouin, Marie Jose
Cantley, Lewis C
Guarente, Leonard
Blenis, John
Pollak, Michael N
Olumi, Aria F
Vander Heiden, Matthew G
Stephanopoulos, Gregory # ×
Issue Date: Jul-2013
Publisher: Waverly Press
Series Title: Cancer Research vol:73 issue:14 pages:4429-38
Article number: 10.1158/0008-5472.CAN-13-0080
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.
ISSN: 0008-5472
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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