IN SILICO STUDIES OF FLAVONOID’S PATTERN OF INHIBITION AGAINST WNT/ β-CATENIN CASCADE

Abstract

The Wnt signaling system is an intricate network of cellular communication pathway that is crucial for tissue homeostasis, development, and disease. It is named after a family of secreted proteins called Wnts, which binds to the receptor on the cellular surface to activate intracellular signaling cascades. This system has vital role in growth related conditions and tumours, particularly as a main factor in proliferation and spread of colorectal cancer (CRC), which is correlated with the build-up of β-catenin in cells due to glycogen synthase kinase-3β (GSK-3β) inactivation. Recently, several polyphenolic substances from the naturally occurring flavonoid family were examined for their potential to inhibit Wnt signaling and found that they exhibit potent anti-oxidant and anti-carcinogenic activities. This thesis identifies the mechanism by which the flavonoids like silibinin, eriodictyol and quercetin attaches to β-catenin and Wnt protein, determining more effective natural inhibitor of the disease-causing protein. For clarify the binding efficiency of flavonoids, a comparative molecular docking analysis was carried out and their interaction with the respective protein molecule is done in this study