Abstract 5381: A novel strategy to eliminate chemoresistant colon cancer cells

Abstract

Abstract Recurrence of colon cancer, which affects nearly 50% of patients treated by conventional therapeutics, is thought to be due to re-emergence of chemotherapy-resistant cancer stem/stem-like cells (CSCs) Therefore, development of therapeutic strategies for targeted elimination of CSCs would be a novel treatment strategy for colon cancer. The current study examines whether diflourinated-curcumin (CDF), a novel analog of the dietary ingredient of curcumin, in combination with 5-fluorouracil and oxaliplatin (5-FU+Ox), the mainstay of colon cancer chemotherapeutic, would be an effective strategy to eliminate colon CSCs. Multiple molecular techniques that include real-time RT-PCR, Western blot analysis, MTT assay, caspase-3 activity, colonosphere formation in stem cell media, Hoechst-33342 dye exclusion and NF-κB-ELISA, were used. We observed that CDF together with 5-FU+Ox to be more potent than curcumin in reducing CD44 and CD166 expression. This was accompanied by inhibition of cell growth, induction of apoptosis and disintegration of colonospheres. These changes were associated with down-regulation of the membrane transporter protein ABCG2, and attenuation of EGFR, IGF-1R, and NF-κB signaling consistent with inactivation of β-catenin, COX-2, c-Myc and Bcl-xL and activation of the pro-apoptotic Bax. Our results suggest that CDF together with the conventional chemotherapeutics could be an effective treatment strategy for preventing the emergence of chemo-resistant colon cancer cells by eliminating CSCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5381. doi:10.1158/1538-7445.AM2011-5381