Phytochemicals attenuating aberrant activation of ?-catenin in cancer cells.

ABSTRACT: Phytochemicals are a rich source of chemoprevention agents but their effects on modulating the Wnt/?-catenin signaling pathway have remained largely uninvestigated. Aberrantly activated Wnt signaling can result in the abnormal stabilization of ?-catenin, a key causative step in a broad spectrum of cancers. Here we report the modulation of lithium chloride-activated canonical Wnt/?-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 ?-catenin degradation, suppression of ?-catenin nuclear localization and down-regulation of downstream oncogenic targets of Wnt/?-catenin pathway. Our study shows a novel degradation path of ?-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.

SUBMITTER: Wang D 

PROVIDER: S-EPMC3513294 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature