Sulforaphane Bioavailability and Chemopreventive Activity in Men Presenting for Biopsy of the Prostate Gland: A Randomized Controlled Trial

Nutr Cancer. 2020;72(1):74-87. doi: 10.1080/01635581.2019.1619783. Epub 2019 Jun 1.

Abstract

Previous studies suggest compounds such as sulforaphane (SFN) derived from cruciferous vegetables may prevent prostate cancer development and progression. This study evaluated the effect of broccoli sprout extract (BSE) supplementation on blood histone deacetylase (HDAC) activity, prostate RNA gene expression, and tissue biomarkers (histone H3 lysine 18 acetylation (H3K18ac), HDAC3, HDAC6, Ki67, and p21). A total of 98 men scheduled for prostate biopsy were allocated into either BSE (200 µmol daily) or a placebo in our double-blind, randomized controlled trial. We used nonparametric tests to evaluate the differences of blood HDAC activity and prostate tissue immunohistochemistry biomarkers between treatment groups. Further, we performed RNA-Seq analysis on the prostate biopsies and identified 40 differentially expressed genes correlated with BSE treatment, including downregulation of two genes previously implicated in prostate cancer development, AMACR and ARLNC1. Although urine and plasma SFN isothiocyanates and individual SFN metabolites were statistically higher in the treatment group, our results did not show a significant difference in HDAC activity or prostate tissue biomarkers. This study indicates BSE supplementation correlates with changes in gene expression but not with several other prostate cancer biomarkers. More research is required to fully understand the chemopreventive effects of BSE supplementation on prostate cancer.

Trial registration: ClinicalTrials.gov NCT01265953.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Anticarcinogenic Agents / administration & dosage
  • Biological Availability
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Brassica*
  • Chemoprevention / methods*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Double-Blind Method
  • Histone Deacetylases / blood
  • Humans
  • Isothiocyanates / administration & dosage*
  • Isothiocyanates / urine
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Prostate / drug effects*
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Neoplasms / diet therapy
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / prevention & control*
  • Racemases and Epimerases / metabolism
  • Vegetable Products / standards

Substances

  • Anticarcinogenic Agents
  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Isothiocyanates
  • Ki-67 Antigen
  • MKI67 protein, human
  • Histone Deacetylases
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase
  • sulforaphane

Associated data

  • ClinicalTrials.gov/NCT01265953