Document Detail

Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G2/M phase cell cycle arrest, DNA damage, and G2/M checkpoint activation.
MedLine Citation:
PMID:  15514285     Owner:  NLM     Status:  MEDLINE    
Benzyl isothiocyanate and phenethyl isothiocyanate, two aromatic phytochemicals present in substantial concentrations in edible vegetables of the genus Brassica, were investigated for their effects on Caco-2 cell proliferation. Benzyl and phenethyl isothiocyanate inhibited DNA synthesis, with 50% inhibitory concentrations of 5.1 and 2.4 micromol/L, respectively, and significantly increased the doubling times of Caco-2 cells from 32 h to 220 and 120 h, respectively. There was no adverse effect of either chemical on cell viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, but benzyl isothiocyanate and phenethyl isothiocyanate both caused an accumulation of cells in the G(2)/M phase of the cell cycle, which was maintained for at least 48 h in cells synchronized at prometaphase with nocodazole and subsequently treated with 10 micromol/L benzyl isothiocyanate or phenethyl isothiocyanate. Both benzyl and phenethyl isothiocyanate increased DNA strand breakage, increased phosphorylation of the G(2)/M checkpoint enforcer Chk2, and induced p21 expression. These results suggest that the antiproliferative effects of benzyl and phenethyl isothiocyanates toward Caco-2 cells are due at least in part to the activation of the G(2)/M DNA damage checkpoint, and that sustained G(2)/M phase cell cycle arrest in response to benzyl and phenethyl isothiocyanates may be maintained through upregulation of p21. This study indicates that some dietary isothiocyanates may exert an antiproliferative effect through activation of the G(2)/M DNA damage checkpoint.
James M Visanji; Susan J Duthie; Lynn Pirie; David G Thompson; Philip J Padfield
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of nutrition     Volume:  134     ISSN:  0022-3166     ISO Abbreviation:  J. Nutr.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-29     Completed Date:  2004-12-09     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3121-6     Citation Subset:  IM    
Section of Gastrointestinal Science, University of Manchester, Manchester, UK.
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MeSH Terms
Brassica / chemistry*
Caco-2 Cells
Cell Division / drug effects*
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / analysis
DNA Damage / drug effects*
Flow Cytometry
G2 Phase / drug effects*
Isothiocyanates / pharmacology*
Protein-Serine-Threonine Kinases / metabolism
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Isothiocyanates; 2257-09-2/phenethyl isothiocyanate; 622-78-6/benzyl isothiocyanate; EC kinase 2; EC Kinases

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