Mechanism of Action of Natural Products against Topoisomerase II
Topoisomerase II is a ubiquitous enzyme that removes knots and tangles from the genetic material. In order to carry out these physiological functions, the enzyme generates transient double-stranded breaks in the DNA. Thus, while essential to cell survival, topoisomerase II has the potential to fragment the genome.
Beyond its critical cellular functions, topoisomerase II is the target for a number of widely prescribed anticancer drugs and dietary chemopreventative agents that act by increasing levels of enzyme-mediated DNA strand breaks. Many of these compounds are derived from natural sources. My research focuses on characterizing the mechanism by which a select group of natural products converts human topoisomerase II into a cellular toxin.