title: Phytochemicals attenuating aberrant activation of β-catenin in cancer cells.
abstract: Phytochemicals are a rich source of chemoprevention agents but their effects on modulating the Wnt/β-catenin signaling pathway have remained largely uninvestigated. Aberrantly activated Wnt signaling can result in the abnormal stabilization of β-catenin, a key causative step in a broad spectrum of cancers. Here we report the modulation of lithium chloride-activated canonical Wnt/β-catenin signaling by phytochemicals that have antioxidant, anti-inflammatory or chemopreventive properties. The compounds were first screened with a cervical cancer-derived stable Wnt signaling reporter HeLa cell line. Positive hits were subsequently evaluated for β-catenin degradation, suppression of β-catenin nuclear localization and down-regulation of downstream oncogenic targets of Wnt/β-catenin pathway. Our study shows a novel degradation path of β-catenin protein in HeLa cells by Avenanthramide 2p (a polyphenol) and Triptolide (a diterpene triepoxide), respectively from oats and a Chinese medicinal plant. The findings present Avenanthramide 2p as a potential chemopreventive dietary compound that merits further study using in vivo models of cancers; they also provide a new perspective on the mechanism of action of Triptolide.
authors.affiliation: Department of Health and Nutritional Sciences, South Dakota State University, Brookings, South Dakota, United States of America.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Wise
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Moul
authors.initials: M
authors.lastname: Dey
mesh_terms: D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D051153:Wnt Proteins; D051176:beta Catenin