Abstract
Abstract Colorectal cancer is the third most frequently occurring cancer in both men and women and is the second leading cause of cancer deaths in the United States. Despite advances in the treatment of this cancer, the five-year averaged survival rate for all stages has only increased to 66% and more than 49,000 deaths of colon cancer in the United States in 2011. Hence, novel therapeutic approaches of more effective treatments are much needed for colon cancer. Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) signaling is frequently detected in human cancer including colon cancer, and has emerged as an attractive molecular target for cancer prevention and therapy. We tested the efficacy of inhibiting persistent STAT3 signaling by a dietary agent, Ursolic acid from basil and a novel STAT3-selective inhibitor, LY5 in human colon cancer cell lines. Our data demonstrated that Ursolic acid is able to inhibit STAT3 phosphorylation, and induce apoptosis in HCT116 and SW480 human colon cancer cell lines. These results were confirmed by LY5, a novel STAT3-selective small molecular inhibitor, which also inhibits STAT3 phosphorylation and induces apoptosis in HCT116 and SW480 colon cancer cell lines. In addition, LY5 inhibits IL-6 mediated induction of STAT3 phosphorylation in DLD-1 human colon cancer cells. We also found Ursolic acid decrease cell viability and inhibit the tumorsphere formation of ALDH+/CD133+ colon cancer stem cells. Furthermore, administration daily of Ursolic acid suppressed the HCT116 tumor growth in mice in vivo. In summary, our results suggest that STAT3 is target for colon cancer prevention and inhibition of persistently activated STAT3 using dietary agents or inhibitors may offer an effective prevention approach for colorectal carcinoma. Citation Format: Li Lin, Wenying Yu, Hui Xiao, Wenlong Wang, Chongqiang Zhao, Jiagao Lu, Chenglong Li, Jiayuh Lin. STAT3 as a cancer prevention target in colorectal cancer cells. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B57.
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