Chemopreventive effect of costunolide, a constituent of oriental medicine, on azoxymethane-induced intestinal carcinogenesis in rats.

Abstract

Modifying effects of costunolide, a constituent of oriental medicines, on intestinal carcinogenesis were examined in a rat model using azoxymethane (AOM). A total of 115 male F344 rats, 6 weeks old, were divided into four groups. Group 1 (30 rats) was fed a diet containing costunolide at a concentration of 0.02% for 4 weeks during which time three s.c. injections of AOM (15 mg/kg) were applied, and then kept on a basal diet until the end of the experiment (33 weeks). Group 2 (30 rats) was given AOM as in group 1 and fed the basal diet throughout, without costunolide. Group 3 (25 rats) was administered costunolide at the start of the experiment, but not given the carcinogen. Group 4 (30 rats) received the basal diet alone throughout the experiment and served as a control. Intestinal tumors were seen in groups 1 and 2, their incidence in group 1 (17%) being significantly lower than in group 2 (50%) (P < 0.05). Furthermore, the number of aberrant crypt foci/cm2 of colon in rats of group 1 at the termination of the experiment was significantly smaller than in group 2 (P < 0.01). BrdU labelling indices of S-phase mucosal cells in the colon of rats in group 1 were significantly lower than those in group 2 (3.9 +/- 3.1 vs. 9.1 +/- 4.5, P < 0.005). The present results suggest that the natural sesquiterpene contained in plants which have been used as oriental drugs, could be a promising chemopreventive agent for human intestinal neoplasia.