Calmodulin antagonist W 13 prevents DNA repair after bleomycin treatment of human urological tumor cells growing on extracellular matrix.
1. The combined application of DNA strand-scission agents (bleomycin) and inhibitors of recovery from lethal damage (calmodulin antagonist W-13) could be a novel and potentially important approach to cancer therapy. 2. As determined by alkaline elution, both DNA-DNA and DNA-protein cross-links in bleomycin-treated cells were revealed by the presence of the proteinase K assay. 3. This lethal effect could be potentiated by the addition of calmodulin antagonist W-13 that prevents the repair of DNA strand breaks and DNA cross-links caused by bleomycin. 4. The results indicated that combinations of bleomycin and W-13 were more effective than treatment with either single agent. Isobologram analysis suggests synergistic effect of these drugs. 5. Therefore, the rational use of combinations of DNA-strand-scission agents and inhibitors of recovery from lethal damage based on mechanistic considerations should result with improved therapeutic regimens for the treatment of cancer.
D001761:Bleomycin / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D008297:Male; D013449:Sulfonamides / Q000494:pharmacology*; D014565:Urogenital Neoplasms / Q000378:metabolism*
D002147:Calmodulin; D003432:Cross-Linking Reagents; D013449:Sulfonamides; D001761:Bleomycin; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide