Demystifying the Relationship Between Metformin, AMPK, and Doxorubicin Cardiotoxicity

Frontiers in Cardiovascular Medicine

Cardiovascular Medicine

Tony Nguyen¹  Satoru Kobayashi¹  Akito T. Nicol¹  Mandeep Singh¹  Qiangrong Liang¹  Jaclyn DelPozzo¹  Manrose Singh¹  Jia Wei² 

[1] Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY, United States;Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xian, China;

关键词: doxorubicin;    metformin;    AMPK;    doxorubicin cardiotoxicity;    cardio-oncology;   

DOI  :  10.3389/fcvm.2022.839644

 received in 2021-12-20, accepted in 2022-01-04,  发布年份 2022

来源: Frontiers

【 摘 要 】

Doxorubicin (DOX) is an extremely effective and wide-spectrum anticancer drug, but its long-term use can lead to heart failure, which presents a serious problem to millions of cancer survivors who have been treated with DOX. Thus, identifying agents that can reduce DOX cardiotoxicity and concurrently enhance its antitumor efficacy would be of great clinical value. In this respect, the classical antidiabetic drug metformin (MET) has stood out, appearing to have both antitumor and cardioprotective properties. MET is proposed to achieve these beneficial effects through the activation of AMP-activated protein kinase (AMPK), an essential regulator of mitochondrial homeostasis and energy metabolism. AMPK itself has been shown to protect the heart and modulate tumor growth under certain conditions. However, the role and mechanism of the hypothesized MET-AMPK axis in DOX cardiotoxicity and antitumor efficacy remain to be firmly established by in vivo studies using tumor-bearing animal models and large-scale prospective clinical trials. This review summarizes currently available literature for or against a role of AMPK in MET-mediated protection against DOX cardiotoxicity. It also highlights the emerging evidence suggesting distinct roles of the AMPK subunit isoforms in mediating the functions of unique AMPK holoenzymes composed of different combinations of isoforms. Moreover, the review provides a perspective regarding future studies that may help fully elucidate the relationship between MET, AMPK and DOX cardiotoxicity.

【 授权许可】

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Copyright © 2022 Singh, Nicol, DelPozzo, Wei, Singh, Nguyen, Kobayashi and Liang.