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Cardiomyocyte death in doxorubicin-induced cardiotoxicity

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Doxorubicin (DOX) is one of the most widely used and successful antitumor drugs, but its cumulative and dose-dependent cardiac toxicity has been a major concern of oncologists in cancer therapeutic practice for decades. With the increasing population of cancer survivors, there is a growing need to develop preventive strategies and effective therapies against DOX-induced cardiotoxicity, in particular late-onset cardiomyopathy. Although intensive investigations on DOX-induced cardiotoxicity have continued for decades, the underlying mechanisms responsible for DOX-induced cardiotoxicity have not been completely elucidated. A rapidly expanding body of evidence supports the notion that cardiomyocyte death by apoptosis and necrosis is a primary mechanism of DOX-induced cardiomyopathy and that other types of cell death, such as autophagy and senescence/aging, may participate in this process. This review focuses on the current understanding of the molecular mechanisms underlying DOX-induced cardiomyocyte death, including the major primary mechanism of excess production of reactive oxygen species (ROS) and other recently discovered ROS-independent mechanisms. The different sensitivities to DOX-induced cell death signals between adult and young cardiomyocytes will also be discussed.

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Authors and Affiliations

  1. Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University, School of Medicine, Indianapolis, IN, USA

    Yi-Wei Zhang, Jianjian Shi & Lei Wei

  2. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, P.R. China

    Yi-Wei Zhang, Jianjian Shi, Yuan-Jian Li & Lei Wei

  3. Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University, School of Medicine, R4-370, 1044 West Walnut Str., Indianapolis, IN, 46202-5225, USA

    Lei Wei

  4. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road no. 110, Changsha, 410078, China

    Yuan-Jian Li

Authors
  1. Yi-Wei Zhang
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  2. Jianjian Shi
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  3. Yuan-Jian Li
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  4. Lei Wei
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Corresponding authors

Correspondence to Yuan-Jian Li or Lei Wei.

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Zhang, YW., Shi, J., Li, YJ. et al. Cardiomyocyte death in doxorubicin-induced cardiotoxicity. Arch. Immunol. Ther. Exp. 57, 435–445 (2009). https://doi.org/10.1007/s00005-009-0051-8

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  • DOI: https://doi.org/10.1007/s00005-009-0051-8

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