Phenethyl isothiocyanate, a dual activator of transcription factors NRF2 and HSF1

Sharadha Dayalan Naidu, Takafumi Suzuki, Masayuki Yamamoto, Jed W. Fahey, Albena Dinkova-Kostova (Lead / Corresponding author)

Research output: Contribution to journalReview article

5 Citations (Scopus)
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Abstract

Cruciferous vegetables are rich sources of glucosinolates which are the biogenic precursor molecules of isothiocyanates (ITCs). The relationship between the consumption of cruciferous vegetables and chemoprotection has been widely documented in epidemiological studies. Phenethyl isothiocyanate (PEITC) occurs as its glucosinolate precursor gluconasturtiin in the cruciferous vegetable watercress (Nasturtium officinale). PEITC has multiple biological effects, including activation of cytoprotective pathways, such as those mediated by the transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) and the transcription factor heat shock factor 1 (HSF1), and can cause changes in the epigenome. However, at high concentrations, PEITC leads to accumulation of reactive oxygen species and cytoskeletal changes, resulting in cytotoxicity. Underlying these activities is the sulfhydryl reactivity of PEITC with cysteine residues in its protein targets. This chemical reactivity highlights the critical importance of the dose of PEITC for achieving on target selectivity, which should be carefully considered in the design of future clinical trials.
Original languageEnglish
Article number1700908
Pages (from-to)e1700908
Number of pages9
JournalMolecular Nutrition & Food Research
Volume62
Issue number18
Early online date30 Apr 2018
DOIs
Publication statusPublished - 1 Sep 2018

Fingerprint

isothiocyanates
heat stress
transcription factors
Vegetables
Glucosinolates
glucosinolates
Nasturtium
NF-E2 Transcription Factor
Isothiocyanates
vegetables
Nasturtium officinale
watercress
vegetable consumption
Cysteine
Epidemiologic Studies
Reactive Oxygen Species
epidemiological studies
cysteine
heat shock transcription factor
phenethyl isothiocyanate

Keywords

  • HSF1
  • HSP90
  • KEAP1
  • NRF2
  • PEITC

Cite this

Dayalan Naidu, Sharadha ; Suzuki, Takafumi ; Yamamoto, Masayuki ; Fahey, Jed W. ; Dinkova-Kostova, Albena. / Phenethyl isothiocyanate, a dual activator of transcription factors NRF2 and HSF1. In: Molecular Nutrition & Food Research. 2018 ; Vol. 62, No. 18. pp. e1700908.
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abstract = "Cruciferous vegetables are rich sources of glucosinolates which are the biogenic precursor molecules of isothiocyanates (ITCs). The relationship between the consumption of cruciferous vegetables and chemoprotection has been widely documented in epidemiological studies. Phenethyl isothiocyanate (PEITC) occurs as its glucosinolate precursor gluconasturtiin in the cruciferous vegetable watercress (Nasturtium officinale). PEITC has multiple biological effects, including activation of cytoprotective pathways, such as those mediated by the transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) and the transcription factor heat shock factor 1 (HSF1), and can cause changes in the epigenome. However, at high concentrations, PEITC leads to accumulation of reactive oxygen species and cytoskeletal changes, resulting in cytotoxicity. Underlying these activities is the sulfhydryl reactivity of PEITC with cysteine residues in its protein targets. This chemical reactivity highlights the critical importance of the dose of PEITC for achieving on target selectivity, which should be carefully considered in the design of future clinical trials.",
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Phenethyl isothiocyanate, a dual activator of transcription factors NRF2 and HSF1. / Dayalan Naidu, Sharadha; Suzuki, Takafumi; Yamamoto, Masayuki; Fahey, Jed W.; Dinkova-Kostova, Albena (Lead / Corresponding author).

In: Molecular Nutrition & Food Research, Vol. 62, No. 18, 1700908, 01.09.2018, p. e1700908.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Phenethyl isothiocyanate, a dual activator of transcription factors NRF2 and HSF1

AU - Dayalan Naidu, Sharadha

AU - Suzuki, Takafumi

AU - Yamamoto, Masayuki

AU - Fahey, Jed W.

AU - Dinkova-Kostova, Albena

N1 - Cancer Research UK (GrantNumber(s): C20953/A18644); Biotechnology and Biological Sciences Research Council (GrantNumber(s): BB/L01923X/1)

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Cruciferous vegetables are rich sources of glucosinolates which are the biogenic precursor molecules of isothiocyanates (ITCs). The relationship between the consumption of cruciferous vegetables and chemoprotection has been widely documented in epidemiological studies. Phenethyl isothiocyanate (PEITC) occurs as its glucosinolate precursor gluconasturtiin in the cruciferous vegetable watercress (Nasturtium officinale). PEITC has multiple biological effects, including activation of cytoprotective pathways, such as those mediated by the transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) and the transcription factor heat shock factor 1 (HSF1), and can cause changes in the epigenome. However, at high concentrations, PEITC leads to accumulation of reactive oxygen species and cytoskeletal changes, resulting in cytotoxicity. Underlying these activities is the sulfhydryl reactivity of PEITC with cysteine residues in its protein targets. This chemical reactivity highlights the critical importance of the dose of PEITC for achieving on target selectivity, which should be carefully considered in the design of future clinical trials.

AB - Cruciferous vegetables are rich sources of glucosinolates which are the biogenic precursor molecules of isothiocyanates (ITCs). The relationship between the consumption of cruciferous vegetables and chemoprotection has been widely documented in epidemiological studies. Phenethyl isothiocyanate (PEITC) occurs as its glucosinolate precursor gluconasturtiin in the cruciferous vegetable watercress (Nasturtium officinale). PEITC has multiple biological effects, including activation of cytoprotective pathways, such as those mediated by the transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) and the transcription factor heat shock factor 1 (HSF1), and can cause changes in the epigenome. However, at high concentrations, PEITC leads to accumulation of reactive oxygen species and cytoskeletal changes, resulting in cytotoxicity. Underlying these activities is the sulfhydryl reactivity of PEITC with cysteine residues in its protein targets. This chemical reactivity highlights the critical importance of the dose of PEITC for achieving on target selectivity, which should be carefully considered in the design of future clinical trials.

KW - HSF1

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DO - 10.1002/mnfr.201700908

M3 - Review article

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