Cisplatin, an effective anti-cancer agent, is used for the treatment of various cancers. However, resistance to cisplatin often disrupts chemotherapy, and efforts have been made to identify compounds that enhance sensitivity of cancer cells to this drug. We previously reported that curcumin enhances the sensitivity of the high-level cisplatin-resistant human epidermoid carcinoma cell line, KCP-4. Other phytochemicals, such as corosolic acid, epigallocatechin gallate (EGCG), and noscapine have been reported to enhance the cisplatin sensitivity of lung and ovarian cancer cells, but it is unclear whether they alter cisplatin resistance of KCP-4 cells. There is also no comparative study of the effects of the above-mentioned compounds administered under the same experimental conditions in the same cell line. In this study, we compared the effects of corosolic acid, curcumin, EGCG, and noscapine on cisplatin sensitivity of KCP-4 cells under controlled conditions. Upon administration of the maximum non-toxic concentration of each compound, curcumin, EGCG, and noscapine, but not corosolic acid, could significantly enhance the cisplatin sensitivity of KCP-4 cells, with the greatest improvement identified in curcumin-treated cells. Curcumin and noscapine were found to suppress nuclear factor-kappa B activation, which when undisrupted, contributes to cisplatin resistance in KCP-4 cells. Curcumin also downregulated Bcl-2 and survivin, and EGCG downregulated survivin. Corosolic acid and noscapine however had no significant effect on the expression of Bcl-2, Bcl-xL, and survivin. Our results suggest that of all compounds tested, curcumin could be the most excellent candidate for enhancing the sensitivity of cisplatin-resistant cancer cells.
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