Colon cancer is one of the major causes of cancer mortality in the United States of America. Early detection and prevention are the important alternative approaches to control colon cancer. Recently, substantial attention has been focused on identifying naturally occurring chemopreventive compounds capable of inhibiting early events involved in malignant transformation. Of late, laboratory studies have demonstrated that silibinin exhibits various biological activities and significantly inhibits tumorigenesis at various organ sites in several rodent models. The present study is an attempt to investigate the dose-dependent effect of dietary silibinin on azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation in Fisher 344 male rats. In addition, we analyzed the effect of silibinin on cell proliferation and the induction of apoptosis by immunohistochemical staining during AOM-induced ACF formation. Five-week-old male F344 rats were randomly divided into 12 groups and fed AIN-76A control diet (group 1) or diet supplemented with 0.033, 0.1, 0.33 or 1% (w/w) silibinin (groups 3-6) till the end of the study. Two weeks later, rats in groups 2-11 were given s.c. injection of AOM once a week for 2 weeks at a concentration of 15 mg/kg body weight. Two weeks after the last AOM injection, rats in groups 7-11 were fed with diet containing 0.033, 0.1, 0.33 or 1% silibinin or 0.032% sulindac. Rats in group 12 were fed with diet containing 1% silibinin alone throughout the study. At 16 weeks of age, the rats were sacrificed, and their colons were evaluated for ACF. The results of this study revealed that silibinin significantly (P< 0.001) reduces the total number and crypt multiplicity of AOM-induced ACF formation in a dose-dependent manner. The mean numbers of ACF was decreased by 39 to 65% in groups 3-6 that received pre- and post-initiation of silibinin and by 29 to 55% in groups 7-10 that received post-initiation of silibinin containing diet. Further immunohistochemical staining showed that silibinin also inhibits cell proliferation and induces apoptosis. These findings suggest the possible beneficial activity of silibinin in the early step of colon tumorigenesis, and indicate that silibinin may be a useful candidate agent for colon cancer chemoprevention, and possibly intervention.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA