Epidemiological and experimental studies have suggested that dietary supplementation with
selenium can inhibit the development of
cancers at several organ sites. We have consistently shown that 1, 4-phenylene bis(methylene)
selenocyanate (p-XSC) is a highly effective
cancer chemopreventive agent against the development of chemically induced
cancers in several laboratory animal species. This is the first report describing the preventive effects of p-XSC in an animal model of
familial adenomatous polyposis (FAP) containing a germline mutation of the APC gene. Six-week old male (heterozygous) C57BL/6J-APC(min) or wild-type mice were fed high fat diets containing 0, 10 or 20 p.p.m. p-XSC. After 80 days, the mice were killed and their intestines were excised and evaluated for
polyps. Multiple samples were also harvested from normal appearing small intestine and colon for molecular analysis. Both the mucosa and
polyps from the intestine and colon were assayed for
beta-catenin,
cyclooxygenase (COX)-2 expression and COX
isoform activities. Administration of p-XSC in the diet significantly decreased the rate of formation of small intestinal
tumors (P < 0. 0001) and colon
tumors (P < 0.002) in APC(min) mice. p-XSC produced a dose-dependent inhibition of
tumors in both small intestine (P < 0. 0001) and colon (P < 0.035). Mice fed 20 p.p.m. p-XSC had significantly lower levels of
beta-catenin expression and COX-2 activity in
polyps. These observations demonstrate for the first time that the synthetic organoselenium compound p-XSC possesses antitumor activity against genetically predisposed neoplastic lesions, such as FAP. While the exact mechanism(s) for this antitumor activity of p-XSC remains to be elucidated, it appears that modulation of
beta-catenin expression and COX-2 activity is associated with inhibition of
intestinal polyps.