Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells
- PMID: 17062558
- DOI: 10.1158/0008-5472.CAN-06-1500
Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells
Abstract
Recent population studies provide clues that the use of metformin may be associated with reduced incidence and improved prognosis of certain cancers. This drug is widely used in the treatment of type 2 diabetes, where it is often referred to as an "insulin sensitizer" because it not only lowers blood glucose but also reduces the hyperinsulinemia associated with insulin resistance. As insulin and insulin-like growth factors stimulate proliferation of many normal and transformed cell types, agents that facilitate signaling through these receptors would be expected to enhance proliferation. We show here that metformin acts as a growth inhibitor rather than an insulin sensitizer for epithelial cells. Breast cancer cells can be protected against metformin-induced growth inhibition by small interfering RNA against AMP kinase. This shows that AMP kinase pathway activation by metformin, recently shown to be necessary for metformin inhibition of gluconeogenesis in hepatocytes, is also involved in metformin-induced growth inhibition of epithelial cells. The growth inhibition was associated with decreased mammalian target of rapamycin and S6 kinase activation and a general decrease in mRNA translation. These results provide evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent population studies and justify further work to explore potential roles for activators of AMP kinase in cancer prevention and treatment.
Similar articles
-
Obesity and insulin resistance in breast cancer--chemoprevention strategies with a focus on metformin.Breast. 2011 Oct;20 Suppl 3:S31-5. doi: 10.1016/S0960-9776(11)70291-0. Breast. 2011. PMID: 22015290 Review.
-
Metformin: taking away the candy for cancer?Eur J Cancer. 2010 Sep;46(13):2369-80. doi: 10.1016/j.ejca.2010.06.012. Epub 2010 Jul 23. Eur J Cancer. 2010. PMID: 20656475 Review.
-
The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase.Cancer Prev Res (Phila). 2008 Oct;1(5):369-75. doi: 10.1158/1940-6207.CAPR-08-0081. Cancer Prev Res (Phila). 2008. PMID: 19138981
-
The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level.Oncogene. 2008 Jun 5;27(25):3576-86. doi: 10.1038/sj.onc.1211024. Epub 2008 Jan 21. Oncogene. 2008. PMID: 18212742
-
Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells.Cancer Res. 2007 Nov 15;67(22):10804-12. doi: 10.1158/0008-5472.CAN-07-2310. Cancer Res. 2007. PMID: 18006825
Cited by
-
Estrogen Receptor Is Required for Metformin-Induced Apoptosis in Breast Cancer Cells Under Hyperglycemic Conditions.Breast Cancer (Auckl). 2024 Apr 8;18:11782234241240173. doi: 10.1177/11782234241240173. eCollection 2024. Breast Cancer (Auckl). 2024. PMID: 38779416 Free PMC article.
-
What are the Optimal Systemic Treatment Options for Rhabdomyosarcoma?Curr Treat Options Oncol. 2024 Jun;25(6):784-797. doi: 10.1007/s11864-024-01206-3. Epub 2024 May 16. Curr Treat Options Oncol. 2024. PMID: 38750399 Review.
-
Systematic Investigation of Dose-Dependent Protein Thermal Stability Changes to Uncover the Mechanisms of the Pleiotropic Effects of Metformin.ACS Pharmacol Transl Sci. 2024 Jan 9;7(2):467-477. doi: 10.1021/acsptsci.3c00298. eCollection 2024 Feb 9. ACS Pharmacol Transl Sci. 2024. PMID: 38357277
-
Chemopreventive and Biological Strategies in the Management of Oral Potentially Malignant and Malignant Disorders.Bioengineering (Basel). 2024 Jan 9;11(1):65. doi: 10.3390/bioengineering11010065. Bioengineering (Basel). 2024. PMID: 38247942 Free PMC article. Review.
-
Feasibility and metabolic outcomes of a well-formulated ketogenic diet as an adjuvant therapeutic intervention for women with stage IV metastatic breast cancer: The Keto-CARE trial.PLoS One. 2024 Jan 2;19(1):e0296523. doi: 10.1371/journal.pone.0296523. eCollection 2024. PLoS One. 2024. PMID: 38166036 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials