Molecular chemoprevention by morin - A plant flavonoid that targets nuclear factor kappa B in experimental colon...

Colorectal cancer is the third most common cancer worldwide. The development of effective, inexpensive and safe chemopreventive agents would be of great benefit as it involves use of natural products to prevent or suppress the progression of precursor lesions. Morin a flavonoid found in figs (Ficus carica) and other plants is shown to inhibit 1,2-dimethylhydrazine (DMH) induced colon cancer progression in a short term and long term model of colon cancer rats; however, the molecular target for the colon cancer chemoprotective efficacy of morin is yet to be discovered. The present study aims to explore the molecular basis of how morin contributes to the chemoprevention with a focus on NF-κB signaling pathway. The effect of morin on NF-κB signaling in DMH-induced carcinogenic events such as inflammation and apoptosis were analyzed by studying the histopathological analysis using Hematoxylin and Eosin staining (H &E), mRNA expression using q-PCR, protein expression using Immunohistochemistry (IHC) and western blot. Morin supplementation to DMH administered rats down regulated NF-κB pathway and its downstream inflammatory mediators like tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase 2 (COX-2) and prostaglandin (PGE-2). Morin supplementation to DMH administered rats alters BAX/BCL2 ratio favoring apoptosis in carcinogen treated rats. Our findings explored that molecular chemoprevention of morin targets NF-κB and acts as a potent anti-inflammatory and pro-apoptotic agent for colon cancer prevention.