Inhibition of the DNA catenation activity of type II topoisomerase by VP16-213 and VM26

Biochem Biophys Res Commun. 1984 Jul 18;122(1):165-70. doi: 10.1016/0006-291x(84)90454-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA Topoisomerases, Type I / metabolism
  • DNA, Neoplasm / metabolism
  • Etoposide / pharmacology*
  • Liver Neoplasms, Experimental / enzymology
  • Podophyllotoxin / analogs & derivatives*
  • Rats
  • Structure-Activity Relationship
  • Teniposide / pharmacology*
  • Topoisomerase II Inhibitors*


  • DNA, Neoplasm
  • Topoisomerase II Inhibitors
  • Etoposide
  • Teniposide
  • DNA Topoisomerases, Type I
  • Podophyllotoxin