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 T.
N1 - Funding Information:
The authors thank Dr. Ryota Saito and Mr. Soichiro Asami for their assistance with cell culture and peritoneal macrophage isolation. The authors are also grateful to Cancer Research UK (C20953/A18644), the BBSRC (BB/L01923X/1), and the Lewis B. and Dorothy Cullman Foundation for financial support.
Funding Information:
The authors thank Dr. Ryota Saito and Mr. Soichiro Asami for their assistance with cell culture and peritoneal macrophage isolation. The authors are also grateful to Cancer Research UK (C20953/A18644), the BB-SRC (BB/L01923X/1), and the Lewis B. and Dorothy Cullman Foundation for financial support.
Publisher Copyright:
© 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2018/9
Y1 - 2018/9
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
KW - HSP90
KW - KEAP1
KW - NRF2
KW - PEITC
UR - http://www.scopus.com/inward/record.url?scp=85053712049&partnerID=8YFLogxK
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U2 - 10.1002/mnfr.201700908
DO - 10.1002/mnfr.201700908
M3 - Review article
C2 - 29710398
AN - SCOPUS:85053712049
VL - 62
JO - Die Nahrung
JF - Die Nahrung
SN - 1613-4125
IS - 18
M1 - 1700908
ER -