Molecular mechanisms of natural products on DMH 1 2 dimethyl hydrazine induced colon carcinogenesis in Wistar Rats

Abstract

Cancer is a major public health burden in India and other developed and developing countries causing approximately seven million deaths every year worldwide. Colon cancer is escalating its threat due to the high mortality rate. It is known as the third most common cancer found in men and women, worldwide. Presently, it constitutes approximately 10% of the cancer burden. Colorectal cancer is likely to expand by 60% and gt 2.2 million new cases have been predicted by 2030. Colon carcinogenesis is a multistep process and is thought to arise by the accretion of genetic alterations involving a variety of oncogenes and tumor suppressor genes that transform normal colonic epithelium into an invasive carcinoma with an adenomatous polyp as an intermediate step in this process. Redox imbalance could be the main cause for cellular damage and mutations and has been implicated in various pathological conditions including cancer, thus may be related to oncogenic stimulation, persistent oxidative stress, and inflammation. Dysregulation of the Wnt/and#946;-catenin pathway plays an important role in events in colorectal carcinogenesis. Mutation in APC a tumor suppressor gene directly leads to unrestricted action of the Wnt signaling pathway which inturn enhances beta-catenin accumulation in the nucleus leading to proliferation, inflammation, tumor formation. newlineMany experimental animal models have supported the idea that a high-fat diet augments the incidence of colon carcinogenesis[8] whereas low fat and high fiber (present in fruits and vegetables) diet, decreases the risk of colon cancer[9] Many natural products present in the high fiber diets have been reported to possess chemopreventive properties against cancer[10]. Available treatment of colon cancer is a painful and difficult task to handle. Therefore, chemoprevention by natural compounds (having negligible to no side effects) is gaining popularity in different parts of the world including our own country, hence it may be a logical strategy for the intervention of the process of co