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

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.

Polymeric black tea polyphenols inhibit 1,2-dimethylhydrazine induced colorectal carcinogenesis by inhibiting cell proliferation via Wnt/beta-catenin pathway.

Tea polyphenols like epigallocatechin gallate and theaflavins are established chemopreventive agents for colorectal carcinogenesis. However, studies on evaluating similar chemopreventive properties of thearubigins or polymeric black tea polyphenols (PBPs), the most abundant polyphenols in black tea, are limited. Hence, in the present study we aim to investigate chemopreventive effects along with probable mechanisms of action of PBP extract employing 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in Sprague-Dawley rats as experimental model. The present study suggests that PBPs, like other tea polyphenols, also inhibit DMH-induced colorectal tumorigenesis by decreasing tumor volume and multiplicity. This study also shows that although the pretreatment with PBP extract could induce detoxifying enzymes in hepatic and colorectal tissue, it did not show any additional chemopreventive effects when compared to treatments with PBP extract after initiation with DMH. Mechanistically, PBP extract may inhibit colorectal carcinogenesis by decreasing DMH-induced cell proliferation via Wnt/beta-catenin pathway. Treatments with PBP extract showed decreased levels of COX-2, c-MYC and cyclin D1 proteins which aid cell proliferation probably by regulating beta-catenin by maintaining expression of APC and decreasing inactivation of GSK3beta. DMH-induced activation of MAP kinases such as ERK and JNK was also found to be inhibited by treatments with PBP extract. In conclusion, the protective effects of PBP extract could be attributed to inhibition of DMH-induced cellular proliferation probably through beta-catenin regulation.

Lack of chemopreventive effects of alpha-eleostearic acid on 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH)-induced mammary and colon carcinogenesis in female Sprague-Dawley rats.

alpha-Eleostearic acid is one of the conjugated linolenic acids from tung oil, which is obtained from the seeds of Aleurites fordii. The effects of dietary alpha-eleostearic acid (18:3, n-5) on the post-initiation period of 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH)-induced mammary and colon carcinogenesis were examined using female Sprague-Dawley (SD) rats. For initiation, rats were given subcutaneous injections of 40mg/kg body weight (5 times) and 20mg/kg body weight (3 times) of DMH during the age of 6-8 weeks and a single intragastric administration of 50mg/kg body weight of DMBA at 9 weeks. Then, the animals were treated with 0%, 0.01%, 0.1% or 1.0% alpha-eleostearic acid for 34 weeks. Control rats received the basal diet alone or 1.0% alpha-eleostearic acid without prior initiation treatment. All surviving animals were killed at week 37 of the experiment. There were no statistically significant alterations in any of the parameters for either mammary or colon tumors. These results thus indicate that alpha-eleostearic acid does not exert clear modification effects on DMBA and DMH-induced mammary and colon carcinogenesis, at least under the present experimental conditions.