Resveratrol inhibits intestinal tumorigenesis and modulates host-defense-related gene expression in an animal model of human familial adenomatous polyposis

We studied the effect of oral administration Of resveratrol, a natural cons tituent of grapes, on tumorigenesis in Min mice. Min mice are congenic mice genetically predisposed to develop intestinal tumors as a result of a muta tion of the Ape 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 co ntaining 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 resv eratrol downregulated genes that are directly involved in cell cycle progre ssion or cell proliferation (cyclins DI and D2, DP-1 transcription factor, and Y-box binding protein). In addition, resveratrol upregulated several ge nes that are involved in the recruitment and activation of immune cells (cy totoxic T lymphocyte Ag-4, leukemia inhibitory factor receptor, and monocyt e chemotactic protein 3) and in the inhibition of the carcinogenic process and tumor expansion (tumor susceptibility protein TSG101, transforming grow th factor-beta, inhibin-beta A subunit, and desmocollin 2). Our data highli ght the complexity of the events associated with intestinal tumorigenesis a nd the multiplicity of the molecular targets of resveratrol. The high poten cy and efficacy of resveratrol support its use as a chemopreventive agent i n the management of intestinal carcinogenesis.