The cancer chemopreventive actions of phytochemicals derived from glucosinolates.
This article reviews the mechanisms by which glucosinolate breakdown products are thought to inhibit carcinogenesis. It describes how isothiocyanates, thiocyanates, nitriles, cyano-epithioalkanes and indoles are produced from glucosinolates through the actions of myrosinase, epithiospecifier protein and epithiospecifier modifier protein released from cruciferous vegetables during injury to the plant. The various biological activities displayed by these phytochemicals are described. In particular, their abilities to induce cytoprotective genes, mediated by the Nrf2 (NF-E2 related factor 2) and AhR (arylhydrocarbon receptor) transcription factors, and their abilities to repress NF-kappaB (nuclear factor-kappaB) activity, inhibit histone deacetylase, and inhibit cytochrome P450 are outlined. Isothiocyanates appear to alter gene expression through modification of critical thiols in regulatory proteins such as Keap1 (Kelch-like ECH-associated protein 1) or IKK (IkappaB kinase), causing activation of Nrf2 and inactivation of NF-kappaB, respectively. Certain indoles act as ligands for AhR. Isothiocyanates and indoles are also capable of affecting cell cycle arrest and stimulating apoptosis. The mechanisms responsible for these anti-proliferative responses are discussed.
Hayes
John D
JD
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK. j.d.hayes@dundee.ac.uk
Kelleher
Michael O
MO
Eggleston
Ian M
IM
D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D018890:Chemoprevention; D004032:Diet; D005961:Glucosinolates / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D017879:Isothiocyanates; D009369:Neoplasms / Q000517:prevention & control*; D021381:Protein Transport; D015398:Signal Transduction
D016588:Anticarcinogenic Agents; D018797:Cell Cycle Proteins; D005961:Glucosinolates; D017879:Isothiocyanates