A ferulic acid derivative, ethyl 3-(4 '-geranyloxy-3-methoxyphenyl)-2-propenoate, as a new candidate chemopreventive agent for colon carcinogenesis in the rat

The inhibitory influence of ferulic acid (FA), a rice germ component, and i ts geranylated derivative 3-(4'-geranyloxy-3-methoxyphenyl)-2-propenoate (E GMP) on the post-initiation stage of azoxymethane (AOM)-induced colon carci nogenesis was studied in male F344 rats given two s.c. injections of AOM (1 5 mg/kg body weight) during week 1, Diets containing EGMP or FA at doses of 0.1 or 0.2% were then fed for 3 weeks from week 2 to 5, when the animals w ere sacrificed. The numbers of aberrant crypt foci (ACF) and aberrant crypt s (AC) per rat in the group given 0.2% FA were significantly decreased (P<0 .001) as compared to the AOM alone group. Furthermore, the numbers of ACF a nd AC per rat fed the 0.2% and 0.1% EGMP were significantly reduced (P<0.00 1 and P<0.01, respectively). Colonic epithelial cells in S-phase, as measur ed by bromodeoxyuridine (BrdU) labeling, in rats fed EGMP were significantl y decreased in the 0.2 and 0.1% EGMP groups as compared to the AOM alone gr oup (P<0.05). BrdU labeling indices in rats fed FA and EGMP assessed by a t est using a coefficient far linear contrast were also significantly decreas ed as compared to the AOM alone value (P<0.05, P<0.01, respectively). The r esults indicate that FA and EGMP have inhibitory effects on ACF and AC deve lopment, EGMP being more potent, possibly due to stronger suppressive effec ts on cell proliferation. No toxic effects were observed in rats given eith er compound in terms of body and organ weights, and liver or kidney histolo gy, The findings thus suggest that EGMP and FA, especially the former, migh t have potential as chemopreventive agents against colon tumor development.