Doxorubicin-induced apoptosis: Implications in cardiotoxicity

  • B. Kalyanaraman
  • Joy Joseph
  • Shashi Kalivendi
  • Suwei Wang
  • Eugene Konorev
  • Srigiridhar Kotamraju
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)


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 H202has been shown to be responsible for this drug’s toxicity and apoptosis. H202in 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. (Mol Cell Biochem 234/235: 119–124, 2002)

Key words

doxorubicin apoptosis endothelial nitric oxide synthase caspase activation 


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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • B. Kalyanaraman
    • 1
  • Joy Joseph
    • 1
  • Shashi Kalivendi
    • 1
  • Suwei Wang
    • 1
  • Eugene Konorev
    • 1
  • Srigiridhar Kotamraju
    • 1
  1. 1.Medical College of WisconsinBiophysics Research Institute and Free Radical Research CenterMilwaukeeUSA

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