Synergism from the Combination of Oxaliplatin with Selected Phytochemicals in Human Ovarian Cancer Cell Lines

Oxaliplatin (Oxa) is a third generation platinum drug currently in clinical use for the treatment against colorectal cancer. Although it has a somewhat different spectrum of activity than cisplatin (Cis), it too has two major limitations, namely problems of side-effects and drug resistance. In this study, combined drug action from the combination of Oxa with the phytochemicals andrographolide (Andro), epigallocatechin-3-gallate (EGCG), chlorophyllin (Chl), colchicines (Col), curcumin (Cur) and paclitaxel (Tax) was evaluated in the human ovarian cancer cell lines A2780 and A2780(cisR). The combination index (CI) was used as a measure of synergism (Cl < 1), addictiveness (CI=1) and antagonism (Cl > 1). Generally, all the combinations showed greater synergism at a lower concentration (ED50) than at higher concentrations (ED75 and ED90). Oxa in binary combination with Col and Tax showed the highest synergism in both the cancer cell lines, when administered 4 h after the phytochemical, with CI at ED50 ranging from 0.004 to 0.1. The combination of Oxa with the other phytochemicals generally showed greater synergism when Oxa was administered 4 h before the phytochemical. Appropriately sequenced combination of Oxa with tumor active phytochemicals produces marked synergistic effects in cisplatin resistant as well as nonresistant ovarian cancer cell lines and may offer the means of overcoming drug resistance in ovarian cancer.