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PMID: 23687346 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Cancer research ·Vol. 73 ·No. 14 ·2013-07-15 ·Pages 4429-38

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 L, Blenis J, Pollak MN, Olumi AF, Vander Heiden MG, Stephanopoulos G

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.

MeSH Terms
Animals Cell Line, Tumor Cell Proliferation/drug effects Citric Acid Cycle/drug effects Disease Models, Animal Glucose/metabolism Glutamine/metabolism Male Metformin/pharmacology Mice Mice, Transgenic Oxidation-Reduction Prostatic Neoplasms/drug therapy,metabolism,pathology
Chemicals
Glutamine Metformin Glucose
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Fendt Sarah-Maria
Departments of Chemical Engineering and Biology, Massachusetts Institute of Technology, Cambridge, MA02139, USA.
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
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Article Info
Journal
Cancer research
Abbr.
Cancer Res
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-13-0080
Published
2013-07-15
Epub
2013-00-17
Pages
4429-38
Language
English
Region
United States
NLM ID
2984705R
PMCID
PMC3930683
Subset
IM
Grants
NIDDK NIH HHS · 1R01DK075850-01 · United States
NCI NIH HHS · 1R01CA160458-01A1 · United States
NCI NIH HHS · R01 CA168653 · United States
NCI NIH HHS · 5-P30-CA14051-39 · United States
PHS HHS · 5-P50-090381-09 · United States
NIDDK NIH HHS · R01 DK075850 · United States
NIGMS NIH HHS · R01 GM056203 · United States
NCI NIH HHS · P01 CA120964 · United States
NCI NIH HHS · P30 CA014051 · United States
NIA NIH HHS · R56 AG015339 · United States
NCI NIH HHS · R01 CA160458 · United States
External Links
PubMed source DOI: 10.1158/0008-5472.CAN-13-0080 PMC Full Text View journal details
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