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)

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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

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Keywords

  • HSF1
  • HSP90
  • KEAP1
  • NRF2
  • PEITC

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