Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrin

Streptonigrin, a nonintercalative antitumor Antibiotic, induced mammalian Topoisomerase II dependent DNA cleavage in vitro. The cleavage activity of streptonigrin was comparable to that of demethylepipodophyllotoxin ethylidene-beta-D-glucoside at a low concentration (less than or equal to 10 microM) but one-third lower at a higher concentration (greater than 250 microM). Exposure of a reaction mixture containing streptonigrin, DNA, and Topoisomerase II to an elevated temperature (65 degrees C) resulted in substantial reduction in DNA cleavage, suggesting that the mechanism of the Topoisomerase II dependent DNA cleavage induced by streptonigrin was through the formation of a cleavage complex previously reported for Topoisomerase II poisons such as 4'-(9-acridinylamino) methanesulfon-m-anisidide and epipodophyllotoxins.