Differential proteomics identifies PDIA3 as a novel chemoprevention target in human colon cancer cells
Article first published online: 19 DEC 2012
© 2012 Wiley Periodicals, Inc.
Special Issue: Mechanisms and Targets for Prevention and Treatment of Colorectal Cancer
Volume 53, Issue S1, pages E11–E22, February 2014
How to Cite
Ménoret, A., Drew, D. A., Miyamoto, S., Nakanishi, M., Vella, A. T. and Rosenberg, D. W. (2014), Differential proteomics identifies PDIA3 as a novel chemoprevention target in human colon cancer cells. Mol. Carcinog., 53: E11–E22. doi: 10.1002/mc.21986
- Issue published online: 24 FEB 2014
- Article first published online: 19 DEC 2012
- Manuscript Accepted: 5 NOV 2012
- Manuscript Revised: 24 OCT 2012
- Manuscript Received: 18 JUL 2012
- NIH. Grant Number: 1R01CA125691
- Connecticut Department of Public Health Biomedical Research. Grant Number: DPH 2009-0914
- colon cancer;
Chemoprevention offers a promising strategy to prevent or delay the development of various cancers. Critical to this approach is the identification of molecular targets that may track with chemopreventive efficacy. To address this issue, we screened a panel of chemoprevention agents, including resveratrol, epigallocatechin-3-gallate, ursodeoxycholic acid, and sulindac sulfide for their effects on human colon cancer cell viability. Resveratrol elicited the most potent effect in HCT116 cells and was selected for further study. Proteomic PF 2D maps were generated from HCT116 cells treated with resveratrol versus vehicle alone. Analysis of proteomic maps using tandem mass spectrometry (MS) identified a panel of differentially modified proteins. Two proteins, actin and Hsp60, were previously shown in other cell culture systems to be affected by resveratrol, validating our approach. PDIA3, RPL19, histone H2B and TCP1β were uniquely identified by our proteomic discovery platform. PDIA3 was of particular interest given its potential role in regulating chemosensitivity of cancer cells. Total levels of PDIA3 in HCT116 cells were unchanged following 24 h of resveratrol treatment, confirmed by Western blot analysis. Immunoprecipitation of PDIA3 revealed a new set of client proteins following resveratrol treatment, including α, β, and δ-catenins, and cellular fractionation identified decreased nuclear localization of α-catenin by resveratrol. These data establish differential proteomic mapping as a powerful tool for identifying novel molecular targets of chemopreventive agents. © 2012 Wiley Periodicals, Inc.