Doxorubicin Redox Biology: Redox Cycling, Topoisomerase Inhibition, and Oxidative Stress

  • Hong Zhu School of Osteopathic Medicine, Campbell University, Buies Creek, NC 27506, USA
  • Soumyadeep Sarkar College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA
  • Laura Scott Department of Molecular and Cellular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  • Igor Danelisen School of Osteopathic Medicine, Campbell University, Buies Creek, NC 27506, USA
  • Michael A. Trush Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
  • Zhenquan Jia College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA; Department of Biology, University of North Carolina, Greensboro, NC 27412, USA
  • Y. Robert Li School of Osteopathic Medicine, Campbell University, Buies Creek, NC 27506, USA; College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA; Department of Biology, University of North Carolina, Greensboro, NC 27412, USA; Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Blacksburg, VA 24061, USA; Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
Keywords: Anticancer drug, Doxorubicin, Mitochondrial electron transport chain, Oxidative stress, Reactive oxygen species, Redox biology, Redox cycling, Topoisomerase IIbeta

Abstract

Doxorubicin (also called Adriamycin) is effective in treating a wide range of human cancers and currently considered as one of the most important drugs in cancer chemotherapeutics. The clinical use of doxorubicin is, however, associated with dosage-dependent cardiotoxicity and development of heart failure, which diminish the therapeutic index of this widely used anticancer drug. This article first surveys key research findings on doxorubicin redox biology that may impact its cardiotoxicity as well as anticancer activity. It then discusses emerging concepts, especially the topoisomerase IIb‒p53‒mitochondrion axis that may lead to the development of mechanistically based novel strategies to protect against cardiotoxicity and enhance the effectiveness of doxorubicin therapy.
Published
2016-05-01
How to Cite
Zhu, H., Sarkar, S., Scott, L., Danelisen, I., Trush, M. A., Jia, Z., & Li, Y. R. (2016). Doxorubicin Redox Biology: Redox Cycling, Topoisomerase Inhibition, and Oxidative Stress. Reactive Oxygen Species, 1(3), 189‒198. Retrieved from https://www.aimsci.com/ros/index.php/ros/article/view/40
Section
Review Articles