Abstract
Abstract Colorectal cancer is the third most commonly diagnosed cancer in the United States and may cause about 50,830 deaths in 2013. Therefore, there is an unmet need for new therapeutic strategies. Combination of natural compounds with pharmacological small molecular inhibitors to increase anticancer efficacy while minimizing toxicity is an attractive approach for management of cancer. Curcumin, a natural dietary compound, has been shown to inhibit multiple cancer cell signaling pathways involved in survival, proliferation, apoptosis, angiogenesis and metastasis. FL118, a novel camptothecin derivative and an IAP (inhibitor of apoptosis) inhibitor, significantly attenuates colon cancer cell growth in vitro and tumor growth in vivo. In the current study, we report that curcumin enhances FL118 anti-cancer efficiency in colon cancer cell models. MTT and cell death detection ELISA assays were used for quantification of cell viability and apoptosis, respectively, in colon cancer HCT8 and SW620 cells. The synergistic effect of curcumin in combination with FL118 treatment on colon cancer growth inhibition was further analyzed by the Combination Index (CI) equation developed by Chou-Talalay using a CalcuSyn program (Biosoft, Cambridge, UK). Our data demonstrated that curcumin shows a synergistic growth inhibitory effect with FL118 in multiple colon cancer cells (p<0.05). Furthermore, combinational treatment can significantly enhance apoptotic cell death induced in comparison with either FL118 or curcumin treatment alone (p<0.05). In HCT8 colon cancer cells, a combination of 10µM curcumin with 0.3-20 nM FL118 treatment for 72 h showed a strong synergistic effect (CI < 0.5) in cell growth inhibition. Mechanistically, the combination treatment-enhanced cell growth inhibition and apoptosis are associated with alteration of the expression of cell death and cell cycle related genes. In conclusion, we propose that combination of curcumin with FL118 might provide a novel therapeutic strategy in colon cancer treatment. Citation Format: Xiang Ling, Nishant Gandhi, Boyang Jiao, Dhyan Chandra, Fengzhi Li. Synergistic effect of curcumin on FL118 efficacy in colon cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 802. doi:10.1158/1538-7445.AM2014-802
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