Modulation of genetic and epigenetic biomarkers of colorectal cancer in humans by black raspberries: A phase I pilot study

Li Shu Wang, Mark Arnold, Yi Wen Huang, Christine Sardo, Claire Seguin, Edward Martin, Tim H.M. Huang, Ken Riedl, Steven Schwartz, Wendy Frankel, Dennis Pearl, Yiqing Xu, John Winston, Guang Yu Yang, Gary D. Stoner

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)598-610
Number of pages13
JournalClinical Cancer Research
Volume17
Issue number3
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wang, L. S., Arnold, M., Huang, Y. W., Sardo, C., Seguin, C., Martin, E., Huang, T. H. M., Riedl, K., Schwartz, S., Frankel, W., Pearl, D., Xu, Y., Winston, J., Yang, G. Y., & Stoner, G. D. (2011). Modulation of genetic and epigenetic biomarkers of colorectal cancer in humans by black raspberries: A phase I pilot study. Clinical Cancer Research, 17(3), 598-610. https://doi.org/10.1158/1078-0432.CCR-10-1260