Modulation of genetic and epigenetic biomarkers of colorectal cancer in humans by black raspberries: a phase I pilot study. Clin Cancer Res 2011 Feb 01;17(3):598-610
Date
12/03/2010Pubmed ID
21123457Pubmed Central ID
PMC3076314DOI
10.1158/1078-0432.CCR-10-1260Scopus ID
2-s2.0-79551698515 (requires institutional sign-in at Scopus site) 156 CitationsAbstract
PURPOSE: This study evaluated the effects of black raspberries (BRBs) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes, cell proliferation, apoptosis, angiogenesis, and expression of Wnt pathway genes.
EXPERIMENTAL DESIGN: Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder (60 g/d) for 1-9 weeks. Methylation status of promoter regions of five tumor suppressor genes was quantified. Protein expression of DNA methyltransferase 1 (DNMT1) and genes associated with cell proliferation, apoptosis, angiogenesis, and Wnt signaling were measured.
RESULTS: The methylation of three Wnt inhibitors, SFRP2, SFRP5, and WIF1, upstream genes in Wnt pathway, and PAX6a, a developmental regulator, was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received BRB treatment for an average of 4 weeks, but not in all 20 patients with 1-9 weeks of BRB treatment. This was associated with decreased expression of DNMT1. BRBs modulated expression of genes associated with Wnt pathway, proliferation, apoptosis, and angiogenesis in a protective direction.
CONCLUSIONS: These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum. While demethylation of genes did not occur in colorectal tissues from all treated patients, the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted.
Author List
Wang LS, Arnold M, Huang YW, Sardo C, Seguin C, Martin E, Huang TH, Riedl K, Schwartz S, Frankel W, Pearl D, Xu Y, Winston J 3rd, Yang GY, Stoner GMESH terms used to index this publication - Major topics in bold
AdultAged, 80 and over
Apoptosis
Biomarkers, Tumor
Cell Proliferation
Colorectal Neoplasms
DNA Methylation
Female
Fruit
Genes, Tumor Suppressor
Humans
Male
Middle Aged
Neovascularization, Pathologic
Pilot Projects
Signal Transduction
Wnt Proteins
