DNA Topoisomerase II: Promising Target for Anticancer Drugs

Abstract

Topoisomerase II inhibitors are being researched as targets for the generation of antineoplastic drugs because inhibition of topoisomerase II by theses drugs leads to cell death. Inhibitors bind with topoisomerase molecule thus making the enzyme nonfunctional and converting it into a cellular toxin that fragments the genome. Cancer cells divide more rapidly than normal cells. Thus, cancer cells would be killed preferably instead of normal cells by topoisomerase inhibitors. The inhibitors which decrease the overall activity of this enzyme are called catalytic inhibitors and that increase the level of topoisomerase–DNA-cleaved complexes are called poisons. Topoisomerase poisons are further divided into intercalating and non-intercalating. Phytochemicals have proven to be rich sources of topoisomerase II inhibitors and widely used as anticancer drugs, whereas some are components of human diet and known to act as chemopreventive agents. The present review explains the role of both categories of topoisomerase II inhibitors, viz., catalytic inhibitors and poisons, and their role in cancer chemoprevention.