title: Inhibition of DNA Topoisomerase I by Dihydrotanshinone I, Components of a Medicinal Herb Salvia miltiorrhiza Bunge.
abstract: Dihydrotanshinone I induced topoisomerase I-mediated DNA cleavage in vitro as strongly as camptothecin, but topoisomerase II-mediated DNA cleavage was not affected. In a DNA relaxation assay using calf thymus DNA topoisomerase I and supercoiled pBR322 plasmid DNA, dihydrotanshinone I reduced topoisomerase I-mediated DNA relaxation in a dose-dependent manner. Heat treatment (65°C) of the reaction mixture containing dihydrotanshinone I and topoisomerase I resulted in a substantial reduction in DNA cleavage, suggesting topoisomerase I and dihydrotanshinone I may form a reversible cleavable complex to induce DNA damage. A DNA unwinding assay using T4 DNA ligase showed that dihydrotanshinone I is a very weak DNA intercalator. These results suggest that dihydrotanshinone I inhibits the catalytic activity of topoisomerase I by the formation of a cleavable complex and at least in part through the intercalation into DNA.
authors.affiliation: a Department of Microbiology, College of Natural Science, Kyungpook National University.
authors.forename: D S
authors.initials: DS
authors.lastname: Lee
authors.affiliation: a Department of Microbiology, College of Natural Science, Kyungpook National University.
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.affiliation: b Department of Life Resource Science, College of Natural Science, Andong National University.
authors.forename: G S
authors.initials: GS
authors.lastname: Kwon
authors.affiliation: c Marine Microbiology Research Laboratory, Biological Oceanography Division, Korea Ocean Research & Development Institute (KORDI).
authors.forename: H K
authors.initials: HK
authors.lastname: Lee
authors.affiliation: a Department of Microbiology, College of Natural Science, Kyungpook National University.
authors.forename: J H
authors.initials: JH
authors.lastname: Woo
authors.affiliation: a Department of Microbiology, College of Natural Science, Kyungpook National University.
authors.forename: J G
authors.initials: JG
authors.lastname: Kim
authors.affiliation: a Department of Microbiology, College of Natural Science, Kyungpook National University.
authors.forename: S D
authors.initials: SD
authors.lastname: Hong
keywords: DNA intercalator; DNA topoisomerase I inhibitor; dihydrotanshinone I