Journal of Drug Metabolism & Toxicology
Open Access
ISSN: 2157-7609
+44-20-4587-4809
ISSN: 2157-7609
+44-20-4587-4809
Birandra K Sinha
Immunity, Inflammation and Disease Laboratory, National Institutes of Environmental Health Sciences, NIH, Research Triangle, Park, North Carolina,
Tanzania
Review Article
Is Metabolic Activation of Topoisomerase II Poisons Important In The Mechanism Of Cytotoxicity?
Author(s): Birandra K Sinha and Ronald P MasonBirandra K Sinha and Ronald P Mason
The antitumor drugs doxorubicin and etoposide, a phodophyllotoxin derivative, are clinically active for the treatment of human malignancies. Because of their extreme effectiveness in the clinic, their modes of actions have been the subject of intense research for over several decades both in the laboratory and in the clinic. It has been found that both doxorubicin and etoposide (VP-16) act on topoisomerase II, induce DNA cleavage, and form double-strand breaks, causing tumor cell death. However, both of these drugs also undergo extensive metabolism in tumor cells and in vivo to various reactive intermediates that bind covalently to cellular DNA and proteins. Moreover, both drugs are metabolized to reactive free radicals that induce lipid peroxidation and DNA damage. However, the role of drug activation in the mechanism of cytotoxicity remains poorly defined. In this review, w.. View More»
DOI:
10.4172/2157-7609.1000186