Archivum Immunologiae et Therapiae Experimentalis

, Volume 57, Issue 6, pp 435–445 | Cite as

Cardiomyocyte death in doxorubicin-induced cardiotoxicity

Review

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.

Keywords

cardiomyocyte doxorubicin apoptosis necrosis autophagy 

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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2009

Authors and Affiliations

  1. 1.Riley Heart Research Center, Wells Center for Pediatric ResearchIndiana University, School of MedicineIndianapolisUSA
  2. 2.Department of Pharmacology, School of Pharmaceutical SciencesCentral South UniversityChangshaP.R. China
  3. 3.Riley Heart Research Center, Wells Center for Pediatric ResearchIndiana University, School of MedicineIndianapolisUSA
  4. 4.Department of Pharmacology, School of Pharmaceutical SciencesCentral South UniversityChangshaChina

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