Aberrant canonical Wnt signaling: Phytochemical based modulation

Background: Wnt signaling pathway plays a major role during development like gastrulation, axis formation, organ development and organization of body plan development. Wnt signaling aberration has been linked with various disease conditions like osteoporosis, colon cancer, hair follicle tumor, Leukemia, and Alzheimer's disease. Phytochemicals like flavonoid, glycosides, polyphenols, have been reported to directly target the markers of Wnt signaling in different disease models. Purpose: The study deals in detail about the different phytochemical targeting key players of Wnt signaling pathway in diseases like Cancer, Osteoporosis, and Alzheimer's disease. We have focused on the Pharmacological basis of disease alleviation by phytochemical specifically targeting the Wnt signaling markers in this study. Methods: The study focused on the published articles from the preclinical rodent and invitro cell line studies related to Wnt signaling and Phytochemicals related to Cancer, Alzheimer's and Osteoporosis. The electronic databases Scopus, Web of Science and Pubmed database were used for the systematic search of literatures from 2005 up to 2019 using keywords Canonical Wnt signaling pathway, Cancer, Alzheimer's disease, Osteoporosis, Phytochemicals. The focus was to identify the target specific modulation of Wnt signaling mediated by phytochemicals. Results: Approximately 30 phytochemicals of different class have been identified to modulate Wnt signaling pathway acting through Axin, beta-catenin translocation, GSK-3 beta, AKT, Wif-1 in various experimental studies. The down regulation of Wnt signaling is observed in Cancer mostly colorectal cancer, breast cancer mediated through mutations in APC and Axin genes. Different class of Phytochemicals such as flavonoid, glycosides, polyphenol, alkaloids etc. have been found to target Wnt signaling markers and alleviate Cancer. Similarly, Up regulation of Wnt signaling has been reported in Osteoporosis and neurodegenerative disease like Alzheimer's disease. Conclusion: This review highlights the possibility of the Phytochemicals to target Wnt markers and its potential to either activate or deactivate the Wnt signaling pathway. It also describes the challenges in proper targeting of Wnt signaling and the potential risk and consequences of either up regulation or down regulation of the signaling pathway. This article highlights the possibility of Wnt signaling pathway as a therapeutic option in different diseases.