Relevance of Ferroptosis to Cardiotoxicity Caused by Anthracyclines: Mechanisms to Target Treatments

Frontiers in Cardiovascular Medicine

Priyanka Gokulnath¹  Guoping Li¹  Chao Yuan²  Na An³  Jianzhen Zhang³  Xinyu Yang⁴  Xin Su⁵  Can Liu⁵  Hengwen Chen⁵  Wanli Sun⁵  Yanwei Xing⁵  Guoxia Zhang⁵  Min Wu⁵  Shipeng Sun⁵  Gururaja Vulugundam⁶ 

[1] Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States;Dezhou Second People’s Hospital, Dezhou, China;Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China;Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China;Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China;Institute of Biochemistry and Cellular Biology, National Research Council of Italy, Naples, Italy;

关键词: ferroptosis;    doxorubicin;    iron;    treatment;    mechanism;    cardiotoxicity;   

DOI  :  10.3389/fcvm.2022.896792

来源: DOAJ

【 摘 要 】

Anthracyclines (ANTs) are a class of anticancer drugs widely used in oncology. However, the clinical application of ANTs is limited by their cardiotoxicity. The mechanisms underlying ANTs-induced cardiotoxicity (AIC) are complicated and involve oxidative stress, inflammation, topoisomerase 2β inhibition, pyroptosis, immunometabolism, autophagy, apoptosis, ferroptosis, etc. Ferroptosis is a new form of regulated cell death (RCD) proposed in 2012, characterized by iron-dependent accumulation of reactive oxygen species (ROS) and lipid peroxidation. An increasing number of studies have found that ferroptosis plays a vital role in the development of AIC. Therefore, we aimed to elaborate on ferroptosis in AIC, especially by doxorubicin (DOX). We first summarize the mechanisms of ferroptosis in terms of oxidation and anti-oxidation systems. Then, we discuss the mechanisms related to ferroptosis caused by DOX, particularly from the perspective of iron metabolism of cardiomyocytes. We also present our research on the prevention and treatment of AIC based on ferroptosis. Finally, we enumerate our views on the development of drugs targeting ferroptosis in this emerging field.

【 授权许可】

Unknown