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Mol Cells. 2013 Oct;36(4):279-87. doi: 10.1007/s10059-013-0169-8. Epub 2013 Jun 19.

Metabolic roles of AMPK and metformin in cancer cells.

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1
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, 700-721, Korea.

Abstract

Metformin is one of the most widely used anti-diabetic agents in the world, and a growing body of evidence suggests that it may also be effective as an anti-cancer drug. Observational studies have shown that metformin reduces cancer incidence and cancer-related mortality in multiple types of cancer. These results have drawn attention to the mechanisms underlying metformin's anti-cancer effects, which may include triggering of the AMP-activated protein kinase (AMPK) pathway, resulting in vulnerability to an energy crisis (leading to cell death under conditions of nutrient deprivation) and a reduction in circulating insulin/IGF-1 levels. Clinical trials are currently underway to determine the benefits, appropriate dosage, and tolerability of metformin in the context of cancer therapy. This review highlights fundamental aspects of the molecular mechanisms underlying metformin's anti-cancer effects, describes the epidemiological evidence and ongoing clinical challenges, and proposes directions for future translational research.

PMID:
23794020
PMCID:
PMC3887985
DOI:
10.1007/s10059-013-0169-8
[Indexed for MEDLINE]
Free PMC Article
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