title: Inhibition of the DNA catenation activity of type II topoisomerase by VP16-213 and VM26.
abstract: Studies suggest that the anticancer drugs VP16-213 and VM26 produce cytotoxicity by inducing protein-associated DNA breakage in vivo through interaction with a yet unknown nuclear component. The effects of these drugs and their congeners on topoisomerase activities was investigated. VP16-213, VM26, and congeners active toward inducing DNA breaks also inhibited the catenation activity of eukaryote type II topoisomerase in vitro at very low drug concentrations. A structure-activity relationship was obtained for inhibition of catenation that parallels in vivo DNA breakage and cytotoxic activities. Type I topoisomerase activity was totally unaffected by these drugs.
mesh_terms: D000818:Animals; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D051381:Rats; D013329:Structure-Activity Relationship; D013713:Teniposide / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
chemical_list: D004273:DNA, Neoplasm; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D013713:Teniposide; D004264:DNA Topoisomerases, Type I; D011034:Podophyllotoxin