Abstract
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 A2780cisR. The combination index (CI) was used as a measure of synergism (CI<1), addictiveness (CI=1) and antagonism (CI>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 non-resistant ovarian cancer cell lines and may offer the means of overcoming drug resistance in ovarian cancer.
- Received August 31, 2011.
- Revision received November 2, 2011.
- Accepted November 3, 2011.
- Copyright© 2011 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved