Effect of resveratrol and quercetin alone and in combination on Wnt signaling pathway; Regulators tumor; differentiation dietary intake and weight changes on rat experimental colon carcinoma

Abstract

Backgrounds and Aims: Cancer is one of the most common diseases at the world. 1 out of 8 deaths at the world happen as a result of cancer. Cancer is the third cause of mortality in Iran. Colon cancer is the fourth cause of mortality at the world and annually 1.2million people with the disease are being diagnosed. About 8% of overall mortality rate is associated with colon cancer. Colon cancer has been considerably increased in Iran over the 3 decades and it is the second common cancer in Iran according to annual report of National Cancer Institute of Iran. Spread of colon cancer in Iran can be estimated to 8 out of 100.000people. 3641 new cases of cancer are reported annually in Iran and 2262 people die in Iran every year as a result of colon cancer. Spread of the disease in Iranian population is equal to 22%. accordingly and because of conflicting reports on effectiveness of resveratrol and quercetin in different steps of cancer and lack of existence of study on simultaneous effect of the two compounds on colon cancer in vivo, this study tends to evaluate their effect together, so that positive results obtained from this study can be generalized to human studies. Methods: The present study is designed to investigate the preventive effects of polymeric resveratrol and quercetin on colon carcinogenesis in an azoxymethane-induced rat tumor. Fifty five rats were divided equally into healthy, control, resveratrol, quercetin and combination of resveratrol and quercetin treated groups. Animals received azoxymethane as a carcinogenic agent weekly for two consecutive weeks other than healthy group . They were given resveratrol and quercetin two weeks before till 12 weeks after the last injection of azoxymethane. In the end, histopathological and immunohistochemistry examinations were performed on colon tissue. Results: : The cytological and morphological changes of the cells healthy group were significantly lower compared to other groups that indicates the carcinogenous effect of azoxymethane medicine. Beta-catenin proteins expression was lower in the combination of resveratrol and quercetin group in compare-son with control group (P<0.001). In addition Axin expression was significantly increased in combination of resveratrol and quercetin in comparison with control -treated group (P<0.001). Conclusions: The present study demonstrated the potential anticancer effects combination of resveratrol and quercetin in a typical animal model. The results provide evidence that combination of resveratrol and quercetin exerts a significant chemopreventive effect on AOM-initiated colon cancer through cell proliferation inhibition. More investigations are needed to confirm its safety for human use. Keywords: Colon Cancer, Resveratrol, Quercetin ,Beta-catenin,Axin