Abstract
Abstract Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors therefore COX-1 is now being reconsidered as a target for chemoprevention. Our aim was to examine whether selective COX-1 inhibition could delay or prevent cancer development and clarify the underlying mechanisms. Data clearly showed that COX-1 was required for maintenance of malignant characteristics of colon cancer cells or tumor promoter(s)-induced transformation of pre-neoplastic cells. We also successfully applied a ligand docking computational method to identify a novel selective COX-1 inhibitor, 6-C-(E-phenylethenyl)-naringenin (designated herein as 6CEPN). 6CEPN could bind to COX-1 and specifically inhibit its activity both in vitro and ex vivo. In colorectal cancer cells, it suppressed anchorage-independent growth by inhibiting COX-1 activity. 6CEPN also effectively suppressed tumor growth in a 28-day colon cancer xenograft model without any obvious systemic toxicity. Taken together, COX-1 plays a critical role in human colorectal carcinogenesis, and the specific COX-1 inhibitor merits further investigation as a potential preventive agent against colorectal cancer. Keywords: colon cancer; natural product; cyclooxygenases; signal transduction Note: This abstract was not presented at the meeting. Citation Format: Haitao Li, Feng Zhu, Hanyong Chen, Ka Wing Cheng, Tatyana Zykova, Naomi Oi, Ronald A. Lubet, Ann M. Bode, Mingfu Wang, Zigang Dong. 6-c-(e-phenylethenyl)-naringenin suppresses colorectal cancer growth by inhibiting cyclooxygenase-1. [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 1252. doi:10.1158/1538-7445.AM2014-1252
Published Version
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