Autophagy and mitophagy in the context of doxorubicin-induced cardiotoxicity

Oncotarget. 2017 Jul 11;8(28):46663-46680. doi: 10.18632/oncotarget.16944.

Abstract

Doxorubicin (Dox) is a cytotoxic drug widely incorporated in various chemotherapy protocols. Severe side effects such as cardiotoxicity, however, limit Dox application. Mechanisms by which Dox promotes cardiac damage and cardiomyocyte cell death have been investigated extensively, but a definitive picture has yet to emerge. Autophagy, regarded generally as a protective mechanism that maintains cell viability by recycling unwanted and damaged cellular constituents, is nevertheless subject to dysregulation having detrimental effects for the cell. Autophagic cell death has been described, and has been proposed to contribute to Dox-cardiotoxicity. Additionally, mitophagy, autophagic removal of damaged mitochondria, is affected by Dox in a manner contributing to toxicity. Here we will review Dox-induced cardiotoxicity and cell death in the broad context of the autophagy and mitophagy processes.

Keywords: anthracyclines; heart failure; impaired autophagy and mitophagy; lysosomal dysfunction; oncocardiology.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / therapeutic use
  • Autophagy / drug effects*
  • Biomarkers
  • Cardiotoxicity / diagnosis
  • Cardiotoxicity / etiology*
  • Cardiotoxicity / metabolism
  • Doxorubicin / adverse effects*
  • Doxorubicin / therapeutic use
  • Heart Diseases / diagnosis
  • Heart Diseases / etiology*
  • Heart Diseases / metabolism
  • Humans
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism
  • Mitophagy / drug effects*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Signal Transduction / drug effects

Substances

  • Antibiotics, Antineoplastic
  • Biomarkers
  • Doxorubicin