Phytochemicals Attenuating Aberrant Activation of β-Catenin in Cancer Cells

Phytochemicals are a rich source of chemoprevention agents but their effects on modulating the Wnt/beta-catenin signaling pathway have remained largely uninvestigated. Aberrantly activated Wnt signaling can result in the abnormal stabilization of beta-catenin, a key causative step in a broad spectrum of cancers. Here we report the modulation of lithium chloride-activated canonical Wnt/beta-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 beta-catenin degradation, suppression of beta-catenin nuclear localization and down-regulation of downstream oncogenic targets of Wnt/beta-catenin pathway. Our study shows a novel degradation path of beta-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. Citation: Wang D, Wise ML, Li F, Dey M (2012) Phytochemicals Attenuating Aberrant Activation of beta-Catenin in Cancer Cells. PLoS ONE 7(12): e50508. doi:10.1371/journal.pone.0050508