articleJournal of Clinical InvestigationJan 1, 2014BRONZE OA

Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation

YIYoshihiko IchikawaMGMohsen GhanefarMBMarina BayevaRWRongxue WuAKArineh Khechaduri

Northwestern University · Cleveland Clinic

PubMed
Indexed incrossrefdoajpubmed

Abstract

Doxorubicin is an effective anticancer drug with known cardiotoxic side effects. It has been hypothesized that doxorubicin-dependent cardiotoxicity occurs through ROS production and possibly cellular iron accumulation. Here, we found that cardiotoxicity develops through the preferential accumulation of iron inside the mitochondria following doxorubicin treatment. In isolated cardiomyocytes, doxorubicin became concentrated in the mitochondria and increased both mitochondrial iron and cellular ROS levels. Overexpression of ABCB8, a mitochondrial protein that facilitates iron export, in vitro and in the hearts of transgenic mice decreased mitochondrial iron and cellular ROS and protected against…

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874
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33.89
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100%
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52
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Authors

9

Topics & keywords

Topics
Keywords
  • Cardiotoxicity
  • Doxorubicin
  • Mitochondrion
  • Pharmacology
  • Dexrazoxane
  • Cardiomyopathy
  • Chemistry
  • Cancer research
UN Sustainable Development Goals
  • Good health and well-being
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