Off-target effects of sulforaphane include the derepression of long terminal repeats through histone acetylation events

Scott R. Baier, Richard Zbasnik, Vicki Schlegel, Janos Zempleni

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Sulforaphane is a naturally occurring isothiocyanate in cruciferous vegetables. Sulforaphane inhibits histone deacetylases, leading to the transcriptional activation of genes including tumor suppressor genes. The compound has attracted considerable attention in the chemoprevention of prostate cancer. Here we tested the hypothesis that sulforaphane is not specific for tumor suppressor genes but also activates loci such as long terminal repeats (LTRs), which might impair genome stability. Studies were conducted using chemically pure sulforaphane in primary human IMR-90 fibroblasts and in broccoli sprout feeding studies in healthy adults. Sulforaphane (2.0 μM) caused an increase in LTR transcriptional activity in cultured cells. Consumption of broccoli sprouts (34, 68 or 102 g) by human volunteers caused a dose dependent elevation in LTR mRNA in circulating leukocytes, peaking at more than a 10-fold increase. This increase in transcript levels was associated with an increase in histone H3 K9 acetylation marks in LTR 15 in peripheral blood mononuclear cells from subjects consuming sprouts. Collectively, this study suggests that sulforaphane has off-target effects that warrant further investigation when recommending high levels of sulforaphane intake, despite its promising activities in chemoprevention.

Original languageEnglish (US)
Pages (from-to)665-668
Number of pages4
JournalJournal of Nutritional Biochemistry
Volume25
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • Histone deacetylases
  • Long terminal repeats
  • Off target effects
  • Sulforaphane

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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