The cancer chemopreventive actions of phytochemicals derived from glucosinolates

John D. Hayes, Michael O. Kelleher, Ian M. Eggleston

    Research output: Contribution to journalReview article

    271 Citations (Scopus)

    Abstract

    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 epithio specifier 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-kappa B (nuclear factor-KB) 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 (I kappa B kinase), causing activation of Nrf2 and inactivation of NF-kappa B, 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.

    Original languageEnglish
    Pages (from-to)73-88
    Number of pages16
    JournalEuropean Journal of Nutrition
    Volume47
    DOIs
    Publication statusPublished - May 2008

    Keywords

    • antioxidant response element
    • apoptosis
    • arylhydrocarbon receptor
    • cytochrome P450
    • epithionitriles
    • gene induction glucosinolates
    • glutathione
    • S-transferase
    • isothiocyanates
    • NF-kappa B
    • Nrf2
    • quinone reductase
    • xenobiotic response element
    • ARYL-HYDROCARBON RECEPTOR
    • TRANSCRIPTION FACTOR NRF2
    • CELL-CYCLE ARREST
    • FACTOR-KAPPA-B
    • ANTIOXIDANT RESPONSE ELEMENT
    • GLUTATHIONE S-TRANSFERASES
    • GENE-EXPRESSION PROFILES
    • ISOTHIOCYANATE-INDUCED APOPTOSIS
    • FACTOR E2-RELATED FACTOR-2
    • PROSTATE-CANCER

    Cite this