Inhibitors of DNA topoisomerase I and II isolated from the Coptis rhizomes

A water extract of Coptis chinensis was found to have the ability to stabilize the cleavable complex with mammalian DNA Topoisomerase I. As the result of bioassay-guided fractionation, two protoberberine Alkaloids, epiberberine and groenlandicine, were identified as active principles with Topoisomerase I-mediated DNA cleavage activity in vitro. These two Alkaloids did not induce Topoisomerase II-mediated DNA cleavage. During further examination of the structurally related protoberberine Alkaloids, berberrubine which is produced during the processing of Coptis rhizome as traditional medicine, was identified as a specific inducer of Topoisomerase II-mediated DNA cleavage in vitro. These results indicated that protoberberine Alkaloids are a chemical family which can induce cleavable complexes with topoisomerases I and II.