Synergism from combination of platinum drugs and selected phytochemicals in colorectal cancer

Abstract

Colorectal cancer is the second most leading cause of death among all reported cancer mortality. Chemotherapy is the treatment of choice to treat metastasized colorectal cancer patients. Combined administration of drugs having different mechanism of actions has been demonstrated better efficacy than conventional monotherapy. Epidemiological data suggests that consumption of phytochemicals has a great impact in prevention and treatment of colorectal cancer. In this study four phytochemicals including curcumin, colchicine, EGCG and taxol were combined with cisplatin and oxaliplatin in a binary mode at three different concentrations and sequence of administrations against four different colorectal cancer cell lines (HT-29, CACO-2, LIM-1215 and LIM-2405). When oxaliplatin is combined with curcumin or EGCG, the cytotoxic outcome is more synergistically effective than the combination of cisplatin with either phytochemicals in a binary combination. However, cisplatin in combination with colchicine showed greater synergism than that of oxaliplatin with colchicine. Observed synergisms of the combinations were found to be correlated with platinumDNA binding and cellular accumulations of platinum. DNA damage study indicated that antagonistic combinations were less damaging towards DNA. Proteomic study revealed eleven proteins which displayed significant changes in expression following different drug treatments which were: NPM, ACTB, TBB5, HSP7C, K2CB, GSTP1, GRP78, PSB6, COF1, IDHC and K1C18. Among these proteins NPM and ACTB was considered as antiapoptotic whereas IDHC and K1C18 believed to be proapoptotic.