Resveratrol Inhibits Intestinal Tumorigenesis and Modulates Host-Defense-Related Gene Expression in an Animal Model of Human Familial Adenomatous Polyposis

• Published in: Nutrition and cancer Vol. 39; no. 1; pp. 102 - 107
• Main Authors: Schneider, Yann, Duranton, Benoit, Goss, Francine, Schleiffer, Ren, Seiler, Nikolaus, Raul, Francis
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Lawrence Erlbaum Associates, Inc 01-01-2001; Taylor& Francis
• Subjects: Adenomatous Polyposis Coli - immunology; Adenomatous Polyposis Coli - prevention & control; Animals; Anticarcinogenic Agents - administration & dosage; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Cell Division - drug effects; Disease Models, Animal; Foods and miscellaneous; Gene Expression Regulation - drug effects; Immunity, Cellular - drug effects; Immunity, Cellular - genetics; Intestinal Neoplasms - immunology; Intestinal Neoplasms - prevention & control; Male; Medical sciences; Mice; Mice, Inbred C57BL; Stilbenes - administration & dosage; Treatment Outcome; Tumors; Disease development; Animal model; Treatment efficiency; Rodentia; Gut; Tumorigenicity; Anticarcinogen; Gene expression; Carcinogenesis; Polyposis; Vertebrata; Mammalia; Diet therapy; Mouse; Animal; Resveratrol; Digestive diseases; Intestinal disease; Benign neoplasm
• ISSN: 0163-5581; 1532-7914
• DOI: 10.1207/S15327914nc391_14

We studied the effect of oral administration of resveratrol, a natural constituent of grapes, on tumorigenesis in Min mice. Min mice are congenic mice genetically predisposed to develop intestinal tumors as a result of a mutation of the Apc gene. Resveratrol (0.01% in the drinking water containing 0.4% ethanol) was administered for seven weeks to Min mice starting at five weeks of age. The control group was fed the same diet and received water containing 0.4% ethanol. Resveratrol prevented the formation of colon tumors and reduced the formation of small intestinal tumors by 70%. Comparison of the expression of 588 genes in the small intestinal mucosa showed that resveratrol downregulated genes that are directly involved in cell cycle progression or cell proliferation (cyclins D1 and D2, DP-1 transcription factor, and Y-box binding protein). In addition, resveratrol upregulated several genes that are involved in the recruitment and activation of immune cells (cytotoxic T lymphocyte Ag-4, leukemia inhibitory factor receptor, and monocyte chemotactic protein 3) and in the inhibition of the carcinogenic process and tumor expansion (tumor susceptibility protein TSG101, transforming growth factor-β, inhibin-β A subunit, and desmocollin 2). Our data highlight the complexity of the events associated with intestinal tumorigenesis and the multiplicity of the molecular targets of resveratrol. The high potency and efficacy of resveratrol support its use as a chemopreventive agent in the management of intestinal carcinogenesis.