Abstract
2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG) has been shown to have antioxidative and anti-inflammatory effects. Oxidative and inflammatory reactions are related to the development of colorectal carcinoma (CRC). In the present study, we characterized the preventive activities of THSG on colon carcinogenesis using the azoxymethane- (AOM-) mediated rat colon carcinogenesis model. F344 male rats were randomly divided into 5 groups (untreated and AOM model rats treated with or without THSG at 30, 150, or 250 mg/kg) after which the numbers of aberrant crypt foci (ACF) were assessed in the colon tissues of all rats. The expressions of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), matrix metalloproteinase proteins (MMPs), and carcinoembryonic antigen (CEA) were measured as effective early predictors of CRC using western blot analysis. Treatment with THSG (150 or 250 mg/kg) induced a 50% reduction in total colonic ACF formation (P < 0.05). Furthermore, our results revealed a downregulation of CEA and NF-κB protein levels in the reduced number of ACF elicited by treatment with THSG, whereas levels of COX-2 and MMPs proteins were not changed. Collectively, THSG may be a promising natural lead compound or drug candidate for treating early phases of CRC.
Highlights
Colorectal carcinoma (CRC) is one of the most common tumors in the world and is undoubtedly an important health problem among the Asian population [1]
Necropsy analysis revealed no pathological modifications in gross visual observations of organs including the heart, liver, kidney, and spleen among all groups of rats (Table 2). These results demonstrated that there were no possible adverse side effects or any gross signs of toxicity induced by THSG in AOM-induced aberrant crypt foci (ACF) in rats
These results revealed that COX-2, matrix metalloproteinase proteins (MMPs)-2, and MMP-9 proteins are not associated with the preventive effect of THSG on AOM-induced ACF
Summary
Colorectal carcinoma (CRC) is one of the most common tumors in the world and is undoubtedly an important health problem among the Asian population [1]. To reduce the mortality due to CRC, the search for biomarkers useful for the early detection of CRC is of the utmost importance. Tumor markers, such as matrix metalloproteinase proteins (MMPs) and carcinoembryonic antigen (CEA), reflect tumor biology and have the potential to solve a variety of BioMed Research International. Several studies have shown that the aberrant activation of NF-κB is frequently found in both experimental and human CRC [7, 8], demonstrating that decreased NF-κB levels could be protective against the growth of CRC. Traditional medicinal plants with antioxidant and anti-inflammatory activities have been used for the treatment of AOM-induced ACF [18,19,20]. We investigated whether THSG can exhibit a chemopreventive effect on the AOM-induced CRC model
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