Amplification of anticancer drug-induced DNA damage and apoptosis by DNA-binding compounds

Current Medicinal Chemistry. Anti-cancer Agents
Shosuke Kawanishi, Yusuke Hiraku

Abstract

A number of anticancer drugs exert their effect by causing DNA damage and subsequent apoptosis induction. Most anticancer drugs are known to cause severe side effects. Nontoxic amplification of DNA-cleaving activity of anticancer drugs would enable to reduce drug dose and side effects, leading to development of effective chemotherapy. As a method to approach new cancer chemotherapy, we have investigated the enhancing effects of DNA-binding ligands ("amplifiers"), especially minor groove binders and intercalators, on anticancer drug-induced apoptosis and DNA cleavage, using human cultured cells and(32)P-labeled DNA fragments obtained from the human genes. We have demonstrated as follows: a) DNA-binding molecules (unfused aromatic cations, distamycin A and synthtic triamides) induced amplification of bleomycin-induced DNA cleavage and apoptosis; b) a minor-groove binder distamycin A enhanced duocarmycin A-induced DNA cleavage; c) actinomycin D altered the site specificity of neocarzinostatin-induced DNA cleavage and distamycin A enhanced C1027-induced apoptosis. The mechanism of amplification of DNA cleavage can be explained by assuming that binding of amplifier changes the DNA conformation to allow anticancer drug to interact mo...Continue Reading

Citations

Aug 13, 2011·Science Translational Medicine·Alexander V GasparianKaterina V Gurova
May 18, 2007·Mutation Research·Stephanie M NelsonWilliam A Denny
Sep 15, 2010·Environmental and Molecular Mutagenesis·George R HoffmannJason P Tartaglione
Dec 31, 2005·Bioorganic & Medicinal Chemistry Letters·Yang SongFeng Liang
Nov 18, 2005·Bioorganic & Medicinal Chemistry·Hanping HeXiaoping Cao
Apr 5, 2016·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Bruna L AurasBernardo A Iglesias
Jan 23, 2014·European Journal of Medicinal Chemistry·Antonio RescifinaAntonino Corsaro

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