Phytochemicals Attenuating Aberrant Activation of β-Catenin in Cancer Cells
Open Access
- 3 December 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (12), e50508
- https://doi.org/10.1371/journal.pone.0050508
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.This publication has 49 references indexed in Scilit:
- Receptor Tyrosine Kinases Activate Canonical WNT/β-Catenin Signaling via MAP Kinase/LRP6 Pathway and Direct β-Catenin PhosphorylationPLOS ONE, 2012
- Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic MechanismsExperimental Diabetes Research, 2012
- Modulation of Wnt/ -catenin signaling pathway by bioactive food componentsCarcinogenesis: Integrative Cancer Research, 2011
- Beta-Catenin Accelerates Human Papilloma Virus Type-16 Mediated Cervical Carcinogenesis in Transgenic MicePLOS ONE, 2011
- Wnt signaling through T-cell factor phosphorylationCell Research, 2011
- Isothiocyanates induce oxidative stress and suppress the metastasis potential of human non-small cell lung cancer cellsBMC Cancer, 2010
- The Lack of an Inherent Membrane Targeting Signal Is Responsible for the Failure of the Matrix (M1) Protein of Influenza A Virus To Bud into Virus-Like ParticlesJournal of Virology, 2010
- Dietary phenethylisothiocyanate attenuates bowel inflammation in miceBMC Chemical Biology, 2010
- MyD88-dependent and independent pathways of Toll-Like Receptors are engaged in biological activity of Triptolide in ligand-stimulated macrophagesBMC Chemical Biology, 2010
- MYC-Induced Cancer Cell Energy Metabolism and Therapeutic OpportunitiesClinical Cancer Research, 2009