Colorectal Cancer has now become one of the leading causes of death. Studies indicate that smoking, low physical activities and high-fat diet are a major risk factor for colorectal cancer. Regular intake of high-fat diet can heavily influence obesity and metabolic syndrome by increasing the insulin resistance and inflammatory response which promote carcinogenesis. Previously, it was shown that inhibition of polyol pathway enzyme aldose reductase (AR) prevents carcinogens- and inflammatory growth factors induced CRC. However, the effect of AR inhibition on a high-fat diet (HFD)-induced formation of intestinal polyps in Apc-deficient Min (multiple intestinal neoplasia; ApcMin/+) mice is not known.
To conduct this research, the researchers examined the effect of AR inhibitor, fidarestat on the HFD-induced formation of preneoplastic intestinal polyps in ApcMin/+ mice which is an excellent model of colon cancer.
It was observed that the APCMin/+ mice which were fed for 12 weeks of HFD caused a considerable increase in the formation of polyps in the small and large intestines while the fiderstat given along with the HFD reduced the number of intestinal polyps. Not only that, fiderstat also decreased the size of the polyps in the intestines of HFD treated APC Min mice. Further, the expression levels of beta-catenin, PCNA, PKC-β2, P-AKT, Pp65, COX-2, and iNOS in the small and large intestines of HFD-treated mice significantly increased, and AR inhibitor prevented it. It was concluded that the fiderstat can be used as a potential chemopreventative drug for intestinal cancers due to APC gene mutations.
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Current Cancer Drug Targets