Molecular and Cellular Biochemistry

, Volume 234, Issue 1, pp 119–124 | Cite as

Doxorubicin-induced apoptosis: Implications in cardiotoxicity

  • B. Kalyanaraman
  • Joy Joseph
  • Shashi Kalivendi
  • Suwei Wang
  • Eugene Konorev
  • Srigiridhar Kotamraju


In this review, we discuss the role of nitric oxide synthase in doxorubicin (DOX)-induced cardiomyopathy, a prominent side effect of DOX chemotherapy in cancer patients. It is becoming increasingly clear that apoptosis of myocardial cells plays a critical role in the onset of cardiomyopathy. DOX exposure to endothelial cells and cardiomyocytes caused apoptotic cell death at sub-micromolar concentrations. DOX-induced generation of H2O2 has been shown to be responsible for this drug's toxicity and apoptosis. H2O2 in turn enhanced endothelial nitric oxide synthase (eNOS) transcription in endothelial cells and myocytes. Antisense eNOS depressed DOX-induced oxidative stress and apoptosis. Redox-metal chelators inhibited DOX-induced apoptosis, clearly suggesting a role for reactive oxygen species in DOX-induced apoptosis. Here, we will focus on the role of eNOS expression, iron chelation, and iron signaling on DOX-mediated apoptosis.

doxorubicin reactive oxygen species apoptosis endothelial nitric oxide synthase caspase activation 


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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • B. Kalyanaraman
    • 1
  • Joy Joseph
    • 1
  • Shashi Kalivendi
    • 1
  • Suwei Wang
    • 1
  • Eugene Konorev
    • 1
  • Srigiridhar Kotamraju
    • 1
  1. 1.Biophysics Research Institute and Free Radical Research CenterMedical College of WisconsinMilwaukeeUSA

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