Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism
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 can...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Association for Cancer Research
2014
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| Online Access: | http://hdl.handle.net/1721.1/91508 https://orcid.org/0000-0002-8607-1787 https://orcid.org/0000-0002-6702-4192 https://orcid.org/0000-0002-5410-6543 https://orcid.org/0000-0003-4064-2510 https://orcid.org/0000-0001-6909-4568 https://orcid.org/0000-0003-0701-5275 |
| _version_ | 1826204642649833472 |
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| author | Fendt, Sarah-Maria Bell, Eric L. Keibler, Mark Andrew Davidson, Shawn Michael Wirth, Gregory J. Fiske, Brian Prescott Mayers, Jared R. Schwab, Matthias Bellinger, Gary Csibi, Alfred Patnaik, Akash Blouin, Marie Jose Cantley, Lewis C. Guarente, Leonard Pershing Blenis, John Pollak, Michael N. Olumi, Aria F. Vander Heiden, Matthew G. Stephanopoulos, Gregory |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Fendt, Sarah-Maria Bell, Eric L. Keibler, Mark Andrew Davidson, Shawn Michael Wirth, Gregory J. Fiske, Brian Prescott Mayers, Jared R. Schwab, Matthias Bellinger, Gary Csibi, Alfred Patnaik, Akash Blouin, Marie Jose Cantley, Lewis C. Guarente, Leonard Pershing Blenis, John Pollak, Michael N. Olumi, Aria F. Vander Heiden, Matthew G. Stephanopoulos, Gregory |
| author_sort | Fendt, Sarah-Maria |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:58:40Z |
| format | Article |
| id | mit-1721.1/91508 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:58:40Z |
| publishDate | 2014 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | mit-1721.1/915082022-10-01T12:15:39Z Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism Fendt, Sarah-Maria Bell, Eric L. Keibler, Mark Andrew Davidson, Shawn Michael Wirth, Gregory J. Fiske, Brian Prescott Mayers, Jared R. Schwab, Matthias Bellinger, Gary Csibi, Alfred Patnaik, Akash Blouin, Marie Jose Cantley, Lewis C. Guarente, Leonard Pershing Blenis, John Pollak, Michael N. Olumi, Aria F. Vander Heiden, Matthew G. Stephanopoulos, Gregory Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Fendt, Sarah-Maria Bell, Eric L. Keibler, Mark Andrew Davidson, Shawn Michael Fiske, Brian Prescott Mayers, Jared R. Guarente, Leonard Pershing Vander Heiden, Matthew G. Stephanopoulos, Gregory 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. German Science Foundation (Grant FE1185) National Institutes of Health (U.S.) Glenn Foundation for Medical Research National Institutes of Health (U.S.) (Grant 5-P50-090381-09) National Institutes of Health (U.S.) (Grant 5-P30-CA14051-39) Burroughs Wellcome Fund Smith Family Foundation Damon Runyon Cancer Research Foundation National Institutes of Health (U.S.) (Grant 1R01DK075850-01) National Institutes of Health (U.S.) (Grant 1R01CA160458-01A1) 2014-11-07T19:50:25Z 2014-11-07T19:50:25Z 2013-05 2013-04 Article http://purl.org/eprint/type/JournalArticle 0008-5472 1538-7445 http://hdl.handle.net/1721.1/91508 Fendt, S.-M., E. L. Bell, M. A. Keibler, S. M. Davidson, G. J. Wirth, B. Fiske, J. R. Mayers, et al. “Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism.” Cancer Research 73, no. 14 (May 17, 2013): 4429–4438. https://orcid.org/0000-0002-8607-1787 https://orcid.org/0000-0002-6702-4192 https://orcid.org/0000-0002-5410-6543 https://orcid.org/0000-0003-4064-2510 https://orcid.org/0000-0001-6909-4568 https://orcid.org/0000-0003-0701-5275 en_US http://dx.doi.org/10.1158/0008-5472.can-13-0080 Cancer Research Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research PMC |
| spellingShingle | Fendt, Sarah-Maria Bell, Eric L. Keibler, Mark Andrew Davidson, Shawn Michael Wirth, Gregory J. Fiske, Brian Prescott Mayers, Jared R. Schwab, Matthias Bellinger, Gary Csibi, Alfred Patnaik, Akash Blouin, Marie Jose Cantley, Lewis C. Guarente, Leonard Pershing Blenis, John Pollak, Michael N. Olumi, Aria F. Vander Heiden, Matthew G. Stephanopoulos, Gregory Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism |
| title | Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism |
| title_full | Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism |
| title_fullStr | Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism |
| title_full_unstemmed | Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism |
| title_short | Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism |
| title_sort | metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism |
| url | http://hdl.handle.net/1721.1/91508 https://orcid.org/0000-0002-8607-1787 https://orcid.org/0000-0002-6702-4192 https://orcid.org/0000-0002-5410-6543 https://orcid.org/0000-0003-4064-2510 https://orcid.org/0000-0001-6909-4568 https://orcid.org/0000-0003-0701-5275 |
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