Inhibition of DNA topoisomerase I by dihydrotanshinone I, components of a medicinal herb Salvia miltiorrhiza bunge

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 topoisomeras e I and supercoiled pBR322 plasmid DNA, dihydrotanshinone I reduced topoiso merase I-mediated DNA relaxation in a dose-dependent manner. Heat treatment (65 degrees C) of the reaction mixture containing dihydrotanshinone I and topoisomerase I resulted in a substantial reduction in DNA cleavage, sugges ting topoisomerase I and dihydrotanshinone I may form a reversible cleavabl e complex to induce DNA damage. A DNA unwinding assay using T-4 DNA ligase showed that dihydrotanshinone I is a very weak DNA intercalator. These resu lts suggest that dihydrotanshinone I inhibits the catalytic activity of top oisomerase I by the formation of a cleavable complex and at least in part t hrough the intercalation into DNA.