Combination of 7-hydroxycoumarin in a platinum(IV) complex derived from cisplatin enhanced cytotoxicity with multiple mechanisms of action.

Author(s) Hua, W.; Zhao, J.; Hu, W.; Gou, S.
Journal J Inorg Biochem
Date Published 2018 Sep
Abstract

A novel compound, Cou-platin, composed of 7-hydroxycoumarin and a platinum(IV) moiety derived from cisplatin was designed and synthesized. Significantly, Cou-platin exhibited more potent in vitro antitumor activity against all tested cancer cell lines than that of cisplatin, which was mainly attributed to the liberation of cisplatin and 7-hydroxycoumarin upon reduction with a biomolecular agent. Besides, cellular accumulation of Cou-platin was dramatically increased among several cancer cells in contrast to cisplatin. Flow cytometry study revealed that Cou-platin arrested cell cycle at G2 phase and induced cell apoptosis. Western blots results indicated that it not only activated cell apoptosis pathway, but also inhibited extracellular regulated protein kinases/mitogen-activated protein kinase pathway. In vivo tests showed that Cou-platin, at equimolar dose to cisplatin, could inhibit tumor growth in nude mouse HCT116 tumor xenograft models almost as cisplatin and oxaliplatin, but with less toxicity.

DOI 10.1016/j.jinorgbio.2018.05.015
ISSN 1873-3344
Citation Hua W, Zhao J, Hu W, Gou S. Combination of 7-hydroxycoumarin in a platinum(IV) complex derived from cisplatin enhanced cytotoxicity with multiple mechanisms of action. J Inorg Biochem. 2018;186:17-23.