Fisetin Ameolirates the Azoxymethane and Dextran Sodium Sulfate Induced Colitis Associated Colorectal Cancer

Abstract

Colitis associated colorectal cancer (CAC) is the subtype of colorectal cancer (CRC), CRC is the third most cause of morbidity worldwide. Chronic inflammation caused by oxidative stress is the main risk factor for CAC establishment. Fisetin (3,3’,4’,7 tetrahydroxy flavones) is a dietary flavonoid with major health benefits. This study is aimed to investigate the anti-proliferative effect of Fisetin against azoxymethane (AOM) and Dextran sodium sulfate (DSS) induced CAC. Male Balb/c mice received intraperitoneal injection of AOM (10mg/kg) on day 1, then 2% DSS in drinking water for 7 days followed by drinking water for 14 days and this cycle repeated twice. Mice induced with AOM/DSS received Fisetin (20mg/kg) during the experimental period. On the day 62, animals were sacrificed and the colon was processed for biochemical and histopathological examinations. Diagnostic tumor marker 5’ nucleotidase and γ glutamyl transpeptidase levels were decreased by fisetin treatment. Enzymatic and non-enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, vitamin C and vitamin E depletion due to AOM/DSS induction were brought near to normal by Fisetin. Administeration of fisetin showed a significant increase in the protein expression levels of bax, caspase-3 and decreased expression level of bcl-2 compared with the control group. These results demonstrate that fisetin exhibits chemopreventive and therapeutic effect against CAC.