Cytotoxicity of novel cisplatin analogs in lung, prostate and breast cancer cells

The antitumor agent that is most prescribed for the treatment of cancer is cis-diamminedichloroplatinum (II) (cisplatin), but its application is limited due to toxic side effects; especially nephrotoxicity. Due to these limitations, numerous analogs have been developed. The cytotoxicity of five novel cisplatin analogs, dichloro(4,4\u27-diethyl-2,2\u27-bipyridine)platinum, dichloro(4,4\u27-dipropyl-2,2\u27-bipyridine)platinum, dichloro(4,4\u27-di-t-butyl-2,2\u27-bipyridine)platinum, dichloro(4,4\u27-dimethoxy-2,2\u27-bipyridine)platinum and dichloro[4,4\u27-bis(3-methoxypropyl)-2,2\u27-bipyridine]platinum, in lung (A549), prostate (DU-145) and five breast (MCF-7, MDA-MB-435, MDA-MB-231, DC4 and DB46) cancer cell lines were investigated. Clonogenic survivals demonstrated that these novel analogs were 47 to 242 times more lethal than cisplatin and killed cells predominately by apoptosis. The analogs did not typically cause a block in the cell cycle. Results from clonogenic survivals and calculation of the combination index (CI) revealed that several analogs had slightly synergistic interactions with ionizing radiation to kill prostate and breast cancer cell lines. Results indicate that these novel analogs may be potential antitumor agents in clinical treatment