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 102g) 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.

Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors

“…However, mature broccoli (200 g) intake has been reported to be ineffective in lowering HDAC activity 213 . The lowering of HDAC activity by broccoli supplements in humans has been recently reported to activate p21 and long terminal repeats (LTRs) 214 . In addition, consuming BSE or a diet high on cruciferous vegetables reduced HDAC3 expression in circulating PBMCs and colon biopsies (unpublished data).…”

The andrologist's contribution to a better life for ageing men: part 2

“…They activate the P450 enzyme and promote the oestrogen metabolism towards the nononcogenic 2‐OH‐oestrogens (Morrison et al ., ). Also, broccoli extract is an important source of sulforaphane that has a demethylating effect, favourably influencing the epigenoma (Gibbs et al ., ; Baier et al ., ). Meta‐analysis of epidemiologic studies concludes that the consumption of cruciferous vegetables was inversely associated with the risk of certain cancers (Liu & Lv, ).…”

Myrosinase-treated glucoerucin is a potent inducer of the Nrf2 target gene heme oxygenase 1 — studies in cultured HT-29 cells and mice

“…GL-producing plants also contain a β-thioglucoside glucohydrolase, commonly known as myrosinase (E.C. 3.2.1.147; MYR), which is located in a separate compartment from the GLs [2,6,7]. In addition, there is evidence of MYR activity in the human intestinal microflora [8].…”

“…In addition, there is evidence of MYR activity in the human intestinal microflora [8]. Following the disruption of a plant cell by chewing or cutting, the GLs and MYR react with each other, resulting in the hydrolysis of the β-thioglucoside bond and consequently in the production of equimolar amounts of aglycon, glucose and sulfate [2,7]. Owing to its instability, the aglycon may be rapidly converted into different breakdown products depending on the reaction conditions, such as the pH, the concentration of ferrous ions or the presence of epithiospecifier protein.…”