4.6 Review

A short review: Doxorubicin and its effect on cardiac proteins

Journal

JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 122, Issue 2, Pages 153-165

Publisher

WILEY
DOI: 10.1002/jcb.29840

Keywords

cardiac contractility; cardiotoxicity; doxorubicin; oxidative stress

Funding

  1. Indian Council of Medical Research
  2. Department of Science and Technology [SB/4S/LS107/2013]

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Doxorubicin (DOX) is beneficial for cancer patients, but its toxic effects on the heart can lead to cardiac dysfunction. Oxidative stress induced by DOX disrupts cardiac contractile muscle proteins, affecting the heart's rhythmic mechanism and oxygen consumption rate. This damage to contractile components and associated factors ultimately results in left ventricular ejection and dilation, highlighting the need for clinical markers and medications to address DOX-induced cardiotoxicity.
Doxorubicin (DOX) is a boon for cancer-suffering patients. However, the undesirable effect on health on vital organs, especially the heart, is a limiting factor, resulting in an increased number of patients with cardiac dysfunction. The present review focuses on the contractile machinery and associated factors, which get affected due to DOX toxicity in chemo-patients for which they are kept under life-long investigation for cardiac function. DOX-induced oxidative stress disrupts the integrity of cardiac contractile muscle proteins that alter the rhythmic mechanism and oxygen consumption rate of the heart. DOX is an oxidant and it is further discussed that oxidative stress prompts the damage of contractile components and associated factors, which include Ca(2+)load through Ca(2+)ATPase, SERCA, ryanodine receptor-2, phospholamban, and calsequestrin, which ultimately results in left ventricular ejection and dilation. Based on data and evidence, the associated proteins can be considered as clinical markers to develop medications for patients. Even with the advancement of various diagnosing tools and modified drugs to mitigate DOX-induced cardiotoxicity, the risk could not be surmounted with survivors of cancer.

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