title: Gossypol interferes with both type I and type II topoisomerase activities without generating strand breaks.
abstract: A considerable number of agents with chemotherapeutic potentials reported over the past years were shown to interfere with the reactions of DNA topoisomerases, the essential enzymes that regulate conformational changes in DNA topology. Gossypol, a naturally occurring bioactive phytochemical is a chemopreventive agent against various types of cancer cell growth with a reported activity on mammalian topoisomerase II. The compounds targeting topoisomerases vary in their mode of action; class I compounds act by stabilizing covalent topoisomerase-DNA complexes resulting in DNA strand breaks while class II compounds interfere with the catalytic function of topoisomerases without generating strand breaks. In this study, we report Gossypol as the interfering agent with type I topoisomerases as well. We also carried out an extensive set of assays to analyze the type of interference manifested by Gossypol on DNA topoisomerases. Our results strongly suggest that Gossypol is a potential class II inhibitor as it blocked DNA topoisomerase reactions with no consequently formed strand breaks.
authors.affiliation: Department of Biotechnology, Graduate School of Natural and Applied Sciences, Ege University, Izmir, Turkey.
authors.forename: Muge
authors.initials: M
authors.lastname: Senarisoy
authors.forename: Pakize
authors.initials: P
authors.lastname: Canturk
authors.forename: Sevil
authors.initials: S
authors.lastname: Zencir
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Baran
authors.forename: Zeki
authors.initials: Z
authors.lastname: Topcu
mesh_terms: D000818:Animals; D053960:DNA Breaks; D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D004250:DNA Topoisomerases, Type II / Q000737:chemistry*; D004789:Enzyme Activation; D057075:Enzyme Assays; D004795:Enzyme Stability; D006072:Gossypol / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry; D010957:Plasmids / Q000737:chemistry; D059004:Topoisomerase I Inhibitors / Q000737:chemistry; D059005:Topoisomerase II Inhibitors / Q000737:chemistry
chemical_list: D046911:Macromolecular Substances; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D006072:Gossypol