(+)-Catechin inhibits intestinal tumor formation and suppresses focal adhesion kinase activation in the Min/+ mouse

Colorectal cancer is sensitive to dietary influences. Epidemiological data linking high intake of fruits and vegetables to decreased cancer risk have prompted the search for specific plant constituents implicated in tumor pre vention. This task is difficult because of the complex chemical composition of plant foods and the multifactorial nature of carcinogenesis. Researcher s are aided in this effort by the C57BL/6J-Min/+ (Min/+) mouse, an animal h earing a germline defect in Apc that is similar to the initiating genetic e vent in the majority of human colorectal cancers. In this study, we treated Min/+ mice with (+)-catechin, a phenolic antioxidant abundant in certain f ruits. Administration of (+)-catechin in an AIN-76A diet at doses of 0.1 an d 1% decreased the intestinal tumor number by 75 and 71%, respectively. Mec hanistic studies linked this effect to (+)-catechin-induced changes in inte grin-mediated intestinal cell-survival signaling, including structural alte ration of the actin cytoskeleton and decreased focal adhesion kinase (FAK) tyrosine phosphorylation. Immunoblot analysis of small intestine scrapings from Min/+ mice and Apc(+/+) wild-type C57BL/6J littermates together with e xcised Min/+ adenomas showed increased expression of phosphorylated FAK in the macroscopically normal enterocytes of untreated Min/+ mice and adenomas . Confirming the relevance of this signaling pathway, treatment of Min/+ mi ce with (+)-catechin reduced the expression of phosphorylated FAK to a leve l similar to the wild-type littermate controls. Thus, the natural abundance and favorable bioavailability of (+)-catechin make it a promising addition to the list of potential colorectal cancer chemopreventive agents.