title: Off-target effects of sulforaphane include the derepression of long terminal repeats through histone acetylation events.
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.
authors.affiliation: Department of Nutrition, University of Nebraska-Lincoln, Lincoln, NE.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Baier
authors.affiliation: Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE.
authors.forename: Richard
authors.initials: R
authors.lastname: Zbasnik
authors.affiliation: Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE.
authors.forename: Vicki
authors.initials: V
authors.lastname: Schlegel
authors.affiliation: Department of Nutrition, University of Nebraska-Lincoln, Lincoln, NE. Electronic address: jzempleni2@unl.edu.
authors.forename: Janos
authors.initials: J
authors.lastname: Zempleni
mesh_terms: D000107:Acetylation; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D001937:Brassica / Q000009:adverse effects; D002478:Cells, Cultured; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D018520:Plant Shoots / Q000009:adverse effects; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D013454:Sulfoxides; D020079:Terminal Repeat Sequences; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D017879:Isothiocyanates; D012333:RNA, Messenger; D013454:Sulfoxides; C016766:sulforaphane
keywords: Histone deacetylases; Long terminal repeats; Off target effects; Sulforaphane
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