(+)-Catechin inhibits intestinal tumor formation and suppresses focal adhesion kinase activation in the min/+ mouse
| Autor: | M J, Weyant, A M, Carothers, A J, Dannenberg, M M, Bertagnolli |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Integrins
Stereoisomerism 3T3 Cells Protein-Tyrosine Kinases Catechin Enzyme Activation Mice Inbred C57BL Mice Enterocytes Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Intestinal Neoplasms Tumor Cells Cultured Animals Anticarcinogenic Agents Humans Tyrosine Female Neoplasm Invasiveness Phosphorylation Cell Division Cytoskeleton Signal Transduction |
| Zdroj: | Cancer research. 61(1) |
| ISSN: | 0008-5472 |
| Popis: | 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 prevention. This task is difficult because of the complex chemical composition of plant foods and the multifactorial nature of carcinogenesis. Researchers are aided in this effort by the C57BL/6J-Min/+ (Min/+) mouse, an animal bearing a germline defect in Apc that is similar to the initiating genetic event in the majority of human colorectal cancers. In this study, we treated Min/+ mice with (+)-catechin, a phenolic antioxidant abundant in certain fruits. Administration of (+)-catechin in an AIN-76A diet at doses of 0.1 and 1% decreased the intestinal tumor number by 75 and 71%, respectively. Mechanistic studies linked this effect to (+)-catechin-induced changes in integrin-mediated intestinal cell-survival signaling, including structural alteration 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 excised 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/+ mice with (+)-catechin reduced the expression of phosphorylated FAK to a level 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. |
| Databáze: | OpenAIRE |
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