PMID- 26066520
OWN - NLM
STAT- MEDLINE
DCOM- 20150921
LR  - 20220318
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 334
DP  - 2015 Aug 6
TI  - The selective cytotoxicity of the alkenyl glucosinolate hydrolysis products and 
      their presence in Brassica vegetables.
PG  - 59-71
LID - S0300-483X(15)00110-9 [pii]
LID - 10.1016/j.tox.2015.06.002 [doi]
AB  - Cruciferous vegetable consumption correlates with reduced risk of cancer. This 
      chemopreventative activity may involve glucosinolates and their hydrolysis 
      products. Glucosinolate-derived isothiocyanates have been studied for their 
      toxicity and chemopreventative properties, but other hydrolysis products 
      (epithionitriles and nitriles) have not been thoroughly examined. We report that 
      these hydrolysis products differ in their cytotoxicity to human cells, with 
      toxicity most strongly associated with isothiocyanates rather than 
      epithionitriles and nitriles. We explored mechanisms of this differential 
      cytotoxicity by examining the role of oxidative metabolism, oxidative stress, 
      mitochondrial permeability, reduced glutathione levels, cell cycle arrest and 
      apoptosis. 2-Propenylisothiocyanate and 3-butenylisothiocyanate both inhibited 
      cytochome P450 1A (CYP1A) enzyme activity in CYP expressing MCL-5 cells at high 
      cytotoxic doses. Incubation of MCL-5 cells with non-cytotoxic doses of 
      2-propenylisothiocyanate for 24h resulted in a dose-dependent inhibition of 
      ethoxyresorufin O-deethylase, yet failed to affect CYP1A1 mRNA expression 
      indicating interference with enzyme activity rather than inhibition of 
      transcription. Increased reactive oxygen species (ROS) production was observed 
      only for 2-propenylisothiocyanate treatment. 2-Propenylisothiocyanate treatment 
      lowered reduced glutathione levels whereas no changes were noted with 
      3,4-epithiobutylnitrile. Cell cycle analysis showed that 2-propenylisothiocyanate 
      induced a G2/M block whereas other hydrolysis products showed only marginal 
      effects. We found that 2-propenylisothiocyanate and 3-butenylisothiocyanate 
      induced cell death predominantly via necrosis whereas, 3,4-epithiobutylnitrile 
      promoted both necrosis and apoptosis. Thus the activity of glucosinolate 
      hydrolysis products includes cytotoxicity that is compound-class specific and may 
      contribute to their putative chemoprotection properties.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Kadir, Nurul H A
AU  - Kadir NH
AD  - Cell and Molecular Biology, Imperial College London, SW7 2AZ, UK; School of Food 
      Sciences and Technology, Universiti Malaysia Terengganu, Malaysia.
FAU - David, Rhiannon
AU  - David R
AD  - Computational and Systems Medicine, Imperial College London, SW7 2AZ, UK.
FAU - Rossiter, John T
AU  - Rossiter JT
AD  - Cell and Molecular Biology, Imperial College London, SW7 2AZ, UK.
FAU - Gooderham, Nigel J
AU  - Gooderham NJ
AD  - Computational and Systems Medicine, Imperial College London, SW7 2AZ, UK. 
      Electronic address: n.gooderham@imperial.ac.uk.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150609
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Cytochrome P-450 Enzyme Inhibitors)
RN  - 0 (Glucosinolates)
RN  - 0 (Isothiocyanates)
RN  - 0 (Nitriles)
RN  - 34424-44-7 (butenylisothiocyanate)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Anticarcinogenic Agents/metabolism/*pharmacology
MH  - Apoptosis/drug effects
MH  - Brassica/*metabolism
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Cytochrome P-450 CYP1A1/antagonists & inhibitors/genetics/metabolism
MH  - Cytochrome P-450 Enzyme Inhibitors/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - G2 Phase Cell Cycle Checkpoints/drug effects
MH  - Glucosinolates/metabolism/*pharmacology
MH  - Glutathione/metabolism
MH  - Humans
MH  - Hydrolysis
MH  - Isothiocyanates/metabolism/*pharmacology
MH  - Mitochondrial Membranes/drug effects/metabolism
MH  - Necrosis
MH  - Nitriles/metabolism/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Permeability
MH  - Time Factors
MH  - Transfection
OTO - NOTNLM
OT  - Brassica
OT  - Chemoprevention
OT  - Cytotoxicity
OT  - Glucosinolate hydrolysis products
EDAT- 2015/06/13 06:00
MHDA- 2015/09/22 06:00
CRDT- 2015/06/13 06:00
PHST- 2015/04/21 00:00 [received]
PHST- 2015/06/03 00:00 [revised]
PHST- 2015/06/05 00:00 [accepted]
PHST- 2015/06/13 06:00 [entrez]
PHST- 2015/06/13 06:00 [pubmed]
PHST- 2015/09/22 06:00 [medline]
AID - S0300-483X(15)00110-9 [pii]
AID - 10.1016/j.tox.2015.06.002 [doi]
PST - ppublish
SO  - Toxicology. 2015 Aug 6;334:59-71. doi: 10.1016/j.tox.2015.06.002. Epub 2015 Jun 
      9.