Chemopreventive effects of Coltect, a novel dietary supplement, alone and in combination with 5-aminosalicylic acid in 1,2-dimethylhydrazine-induced colon cancer in rats

Abstract

Abstract:Objectives: Coltect is a novel dietary supplement containing curcumin, green tea and selenomethionine. Previous reports have suggested that these agents can prevent colorectal cancer (CRC). The present study examined the chemopreventive effect of Coltect alone or combined with 5-aminosalicylic acid (5-ASA) using the 1,2-dimethylhydrazine (DMH) model in rats. Methods: The effect of Coltect was examined on HT-29 CRC cells by growth inhibition assay. Apoptosis was determined by annexin V-FITC/PI staining. Male rats were injected with DMH in vivo and treated with Coltect 150 mg/kg, 5-ASA 50 mg/kg or their combination, by oral gavage. Aberrant crypt foci (ACF) were identified by methylene blue staining. Results: HT-29 cells exhibited a dose-dependent response to Coltect. Part of the growth inhibition can be explained by the induction of mild-moderate apoptosis in cancer cells (28%) compared with the untreated cells (10%). In the in vivo model, the average number of ACF was divided into small (13 crypts) or large (!4 crypts). The Coltect compound reduced the number of small and large ACF similarly to 5-ASA (40% reduction). This reduction was amplified by combining the two agents (70% reduction). Conclusion: Coltect inhibits the growth of colon cancer cells, induces apoptosis and inhibits ACF development. Furthermore, it augments the growth inhibitory effect of 5-ASA in vivo. This may be clinically important since this safe dietary supplement-drug combination can be administered as a chemopreventive regimen for the treatment of CRC.

Lifestyle Modifications and Colorectal Cancer

“…Coltect reduced the number of aberrant crypt foci similarly as 5-aminosalicylic acid by 40 %. The use of both substances resulted in a synergistic effect, reducing the number of aberrant crypt foci by 70 % [ 52 ].…”

Quantitative metabolomics for investigating the value of polyamines in the early diagnosis and therapy of colorectal cancer

“…We chose 10 % (w/v) DMH (1, 2-dimethylhydrazine) saline solutions at doses of 40 mg/kg body weight per animal as our experimental carcinogenesis reagent. DMH is a commonly used chemical carcinogen with selectivity for the colorectum, and it induces a carcinogenic process similar to that of spontaneous human colorectal cancer [ 19 – 21 ]. The CRC group rats were induced with DMH for 20 weeks, and the histopathology of each rat rectum was examined on 4th, 8th, 12th, 16th and 20th weeks after DMH induction (Figure 1 ) From the histopathology of the carcinogenic process induced by DMH, it was concluded that CRC developed from mucosal hyperplasia to invasive carcinoma during our experiment.…”

“…A total of 78 rats were divided into two groups, CRC rats ( n = 48) and normal rats ( n = 30). The CRC rats were given DMH solutions as described previously [ 19 – 20 ]. Briefly, the CRC rats received intraperitoneal injections of DMH solution (DMH dissolved in saline to produce 10 % solutions) at a dosage of 40 mg/kg once a week for 8 weeks.…”

Of mice and men: a novel dietary supplement for the treatment of ulcerative colitis

“…The study was approved by the Institutional Committee for Animal Welfare of the Tel-Aviv Sourasky Medical Center (protocol number 1-12-09). 14 …”

“…13 We have shown that the most effective ratios of the three ingredients for cancer prevention in a rat model are curcumin (500 mg), green tea (250 mg) and selenomethionine (100 µg) (Coltect, Israel). 14 Herein, the efficacy of the combination is shown in the DSS model in mice, and validated in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) model in rats. In the clinical setting our results suggest that Coltect may be an effective treatment in patients experiencing mild-to-moderate UC; however, in order to confirm its clinical efficacy larger trials are required.…”