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P085. Effect of phytoestrogenic dietary supplementation on the progression of chronic intestinal inflammation to cancer in an animal model

M. Principi1, N. De Tullio1, K. Lofano1, M. Pricci1, M.P. Scavo1, G. Piacentino1, A. Contaldo1, V. Neve1, E. Ierardi2, M.C. Comelli3, A. Di Leo1, 1University of Bari, Bari, Italy, 2University of Foggia, Italy, 3CM&D Pharma srl, Padova, Italy

Background

Colorectal cancer (CRC) is increased in inflammatory bowel diseases (IBD). Chemopreventive agents could minimize this risk. Estrogens exert prevention against CRC throught Estrogen Receptor beta (ER-beta) with an inverse relation with the tumor. ER-beta induction may be a target in CRC prevention. Phytoestrogens are dietary compounds with higher binding affinity for ER-beta than ER-alpha. A blend of the dietary phytoestrogens (silymarin and lignan) and non-starch insoluble fibers (Eviendep, CM&D Pharma) has been tested in an experimental mouse model of AOM/DSS induced colitis, to assess the anti-inflammatory and anti-carcinogenetic properties and to verify whether such effect is related to an increased ER-beta expression.

Methods

A known model of dextran sodium sulfate/azoxy­methane induced CRC was used to obtain the best simulation of IBD-related CRC pathogenesis. Seventy-six C57BL/6J male mice were divided into three groups: 35 mice fed a Eviendep-modified diet during the whole carcinogenetic process, 35 fed a standard diet (positive control) and 6 mice with no treatment or modified diet (negative control). Monitoring of colitis and tumorigenesis was performed by a specific video-endoscopic system (Coloview Miniendoscopic System) at 21 weeks. Animals were sacrificed at 22 weeks for histogical and ERs immunohistochemical evaluation. Histological score was: 0 (no dysplasia), 1 (low grade dysplasia), 2 (high grade dysplasia) and 3 (carcinoma).

Results

Mortality rate was of 40–50%. At sacrifice, treated animals showed a decrease in number/volume of polyps and in histological score (p < 0.05 ANOVA-Bonferroni post hoc test). Only 30% of Eviendep-supplemented mice showed at least 1 CRC compared with the 100% of the positive controls. ER-alpha expression was higher in neoplastic tissue than in normal mucosa both in treated and positive control groups, while ER-beta labeling index (LI%) showed a higher value in non-neoplastic tissue of the Eviendep-supplemented group (63.8±4.7) than in positive control (46.6±6.4), resulting similar to the ER-beta LI value of negative controls (54.9±7.9) (p < 0.05 Fisher Exact Test).

Conclusion

Our results suggest a chemopreventive effect of Eviendep on colonic carcinogenesis arising from inflamed tissue, and such an effect associates with an increase ER-beta content in the tissue.