Silibinin modulates biotransforming microbial enzymes and prevents 1,2-dimethylhydrazine-induced preneoplastic changes in experimental colon cancer

Abstract

Chemoprevention directed towards the control of colon carcinogenesis in its early stages should ultimately provide a higher quality of life for people than waiting to treat end-stage disease. Silibinin is a major bioactive compound that is present in the widely consumed dietary supplement Silymarin. The current investigation aimed to explore the effect of the phytochemical silibinin on the suppression of 1,2-dimethylhydrazine-induced colonic preneoplastic changes in a long-term preclinical model. Wistar male rats were divided into six groups: group 1 were control rats, group 2 were control rats that received silibinin alone (50 mg/kg body weight orally everyday), rats in group 3 were injected once weekly with 1,2-dimethylhydrazine (20 mg/kg body weight, subcutaneously 15 times), in addition, group 4 (initiation), group 5 (post initiation) and group 6 (entire period) received silibinin as in group 2. At the end of 32 weeks, the activities of the colonic and faecal biotransforming microbial enzymes were analysed. Modulatory effects were also evaluated using aberrant crypt foci (ACF), dysplastic ACF and tumour incidence as endpoint markers. Silibinin markedly reduced tumour incidence, as compared with the rats treated with unsupplemented 1,2-dimethylhydrazine. The most pronounced inhibition of ACF and dysplastic ACF development was observed in the rats fed with silibinin for the entire period and also during the post initiation period. Silibinin administration also significantly (P<0.05) modulated the biotransforming activity of microbial enzymes. The results of our study suggest that silibinin suppresses 1,2-dimethylhydrazine-induced colon carcinogenesis at various stages and exerts a potential chemopreventive action against colon cancer.