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Mol. Cells 2013; 36(4): 279-287

Published online October 31, 2013

https://doi.org/10.1007/s10059-013-0169-8

© The Korean Society for Molecular and Cellular Biology

Metabolic Roles of AMPK and Metformin in Cancer Cells

Yeon Kyung Choi, and Keun-Gyu Park

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

Received: June 3, 2013; Accepted: June 6, 2013

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.

Keywords AMPK, cancer, LKB1, metformin

Article

Minireview

Mol. Cells 2013; 36(4): 279-287

Published online October 31, 2013 https://doi.org/10.1007/s10059-013-0169-8

Copyright © The Korean Society for Molecular and Cellular Biology.

Metabolic Roles of AMPK and Metformin in Cancer Cells

Yeon Kyung Choi, and Keun-Gyu Park

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

Received: June 3, 2013; Accepted: June 6, 2013

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.

Keywords: AMPK, cancer, LKB1, metformin

Mol. Cells
May 31, 2022 Vol.45 No.5, pp. 273~352
COVER PICTURE
Fe2+ ion depletion-induced expression of BΔGFP at the early stage of leaf development (Choi et al., pp. 294-305).

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