Cellular Targets of Dietary Polyphenol Resveratrol
Abstract
Resveratrol, a grape-derived polyphenol, is a chemopreventive agent shown to suppress androgen-dependent and -refractory prostate cancer (CaP) cell growth, and inhibit prostate specific gene expression. To further elucidate its anti-CaP properties, we advance the hypothesis that resveratrol interacts with specific cellular target proteins, denoted RTPs. This project aims to identify and purify RTPs. Our first approach was to test the ability of [3H]resveratrol to form stable complexes with RTPs based on retention on nitrocellulose filters or chromatography on gel filtration columns. Feasibility of this approach was tested using extracts prepared from LNCaP and PC-3 cells. This approach was unsuccessful possibly due to technical limitations, such as: scarcity of RTPs, low specific activity of labeled resveratrol and difficulties in forming stable [resveratrol. RTP] complexes. An alternative approach involved chemically immobilizing resveratrol on epoxyactivated agarose to generate a biospecific affinity matrix for isolating and purifying RTPs from cell extracts. We have named this affinity chromatography approach ligand-select proteomics (LSP) as it affords a panoramic display of proteins having different binding affinities to resveratrol. By combining LSP with MALDI-TOF mass spectrometry, we have identified dihydronicotinamide riboside:quinone reductase (NQO2) as a distinct RTP from LNCaP and PC3cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA454375
Entities
People
- Joseph M. Wu
Organizations
- New York Medical College