Abstract 2143: Inhibiting fatty acid synthase for chemoprevention of chemically induced colorectal tumors

Abstract

Abstract Purpose: Fatty acid synthase (FAS) is overexpressed in colorectal cancer, and we have investigated the potential use of FAS inhibitors for chemoprevention of colorectal cancer. Experimental Design: Expression of FAS was evaluated in human colorectal lesions and in murine models of colorectal tumorigenesis [AOM and DSS induced colorectal tumors in mice]. Then, the ability of pharmacologic inhibitors of FAS to prevent development of the murine tumors was investigated. Results: Immunohistochemical studies show that human colorectal cancers express high levels of FAS compared with normal tissues, suggesting that FAS might be a target for intervention in colorectal carcinogenesis. FAS is also expressed at high levels in chemically induced murine colorectal tumors, and the numbers and sizes of those murine tumors are significantly reduced by treating carcinogen-exposed mice with berberine include, Chinese traditional drug, Kampo. Conclusions: We conclude that increased levels of FAS are common in human colorectal cancer. Based on studies in mouse models, it seems that inhibiting FAS is an effective strategy in preventing and retarding growth of colorectal tumors that have high expression of this enzyme. Citation Format: Hajime Orita, Sigekazu Tanaka, Hiroshi Maekawa, Mutsumi Sakurada, Tomonori Kushida, Tomoaki Ito, Masahiro Miyazaki, Toshihiko Shiroishi, Koichi Sato. Inhibiting fatty acid synthase for chemoprevention of chemically induced colorectal tumors. [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 2143. doi:10.1158/1538-7445.AM2014-2143