Metformin: its emerging role in oncology
- PMID: 21349801
- DOI: 10.14310/horm.2002.1288
Metformin: its emerging role in oncology
Abstract
Metformin is considered, in conjunction with lifestyle modification, as a first-line treatment modality for type 2 diabetes mellitus (DM). Recently, several clinical studies have reported reduced incidence of neoplastic diseases in DM type 2 patients treated with metformin, as compared to diet or other antidiabetic agents. Moreover, in vitro studies have disclosed significant antiproliferative and proapoptotic effects of metformin on different types of cancer. Metformin acts by activating AMP-activated protein kinase (AMPK), a key player in the regulation of energy homeostasis. Moreover, by activating AMPK, metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) resulting in decreased cancer cell proliferation. Concomitantly, metformin induces activation of LKB1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK. These new encouraging experimental data supporting the anti-cancer effects of metformin urgently require further clinical studies in order to establish its use as a synergistic therapy targeting the AMPK/mTOR signaling pathway.
Similar articles
-
Metformin use and gynecological cancers: A novel treatment option emerging from drug repositioning.Crit Rev Oncol Hematol. 2016 Sep;105:73-83. doi: 10.1016/j.critrevonc.2016.06.006. Epub 2016 Jun 18. Crit Rev Oncol Hematol. 2016. PMID: 27378194 Review.
-
Metformin in cancer therapy: a new perspective for an old antidiabetic drug?Mol Cancer Ther. 2010 May;9(5):1092-9. doi: 10.1158/1535-7163.MCT-09-1186. Epub 2010 May 4. Mol Cancer Ther. 2010. PMID: 20442309 Review.
-
Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway.Am J Respir Cell Mol Biol. 2013 Aug;49(2):241-50. doi: 10.1165/rcmb.2012-0244OC. Am J Respir Cell Mol Biol. 2013. PMID: 23526220
-
Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: a novel target for the antidiabetic drug metformin in pancreatic cancer.Clin Cancer Res. 2010 May 1;16(9):2505-11. doi: 10.1158/1078-0432.CCR-09-2229. Epub 2010 Apr 13. Clin Cancer Res. 2010. PMID: 20388847 Free PMC article.
-
Molecular targets of metformin antitumor action.Pharmacol Rep. 2016 Oct;68(5):918-25. doi: 10.1016/j.pharep.2016.04.021. Epub 2016 May 9. Pharmacol Rep. 2016. PMID: 27362768 Review.
Cited by
-
Metformin Caused Radiosensitivity of Breast Cancer Cells through the Expression Modulation of miR-21-5p/SESN1axis.Asian Pac J Cancer Prev. 2023 Nov 1;24(11):3715-3727. doi: 10.31557/APJCP.2023.24.11.3715. Asian Pac J Cancer Prev. 2023. PMID: 38019229 Free PMC article.
-
Type 2 diabetes mellitus and obesity are independent risk factors for poor outcome in patients with high-grade glioma.J Neurooncol. 2012 Jan;106(2):383-9. doi: 10.1007/s11060-011-0676-4. Epub 2011 Aug 11. J Neurooncol. 2012. PMID: 21833800
-
Antitumor effects of metformin are a result of inhibiting nuclear factor kappa B nuclear translocation in esophageal squamous cell carcinoma.Cancer Sci. 2018 Apr;109(4):1066-1074. doi: 10.1111/cas.13523. Epub 2018 Feb 26. Cancer Sci. 2018. PMID: 29396886 Free PMC article.
-
Metformin increases chemo-sensitivity via gene downregulation encoding DNA replication proteins in 5-Fu resistant colorectal cancer cells.Oncotarget. 2017 May 11;8(34):56546-56557. doi: 10.18632/oncotarget.17798. eCollection 2017 Aug 22. Oncotarget. 2017. PMID: 28915611 Free PMC article.
-
Metformin Modulates Cyclin D1 and P53 Expression to Inhibit Cell Proliferation and to Induce Apoptosis in Cervical Cancer Cell Lines.Asian Pac J Cancer Prev. 2019 Jun 1;20(6):1667-1673. doi: 10.31557/APJCP.2019.20.6.1667. Asian Pac J Cancer Prev. 2019. PMID: 31244286 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous