Induction of cancer chemopreventive enzymes by coffee is mediated by transcription factor Nrf2. Evidence that the coffee-specific diterpenes cafestol and kahweol confer protection against acrolein

Larry G. Higgins, Christophe Cavin, Ken Toh, Masayuki Yamamoto, John D. Hayes

    Research output: Contribution to journalArticle

    87 Citations (Scopus)

    Abstract

    Mice fed diets containing 3% or 6% coffee for 5 days had increased levels of mRNA for NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase class Alpha 1 (GSTA1) of between 4- and 20-fold in the liver and small intestine. Mice fed 6% coffee also had increased amounts of mRNA for UDP-glucuronosyl transferase 1A6 (UGT1A6) and the glutamate cysteine ligase catalytic (GCLC) subunit of between 3- and 10-fold in the small intestine. Up-regulation of these mRNAs was significantly greater in mice possessing Nrf2 (NF-E2 p45 subunit-related factor 2) than those lacking the transcription factor. Basal levels of mRNAs for NQO1, GSTA1, UGT1A6 and GCLC were lower in tissues from nrf2(-/-) mice than from nrf2(+/+) mice, but modest induction occurred in the mutant animals. Treatment of mouse embryonic fibroblasts (MEFs) from nrf2(+/+) mice with either coffee or the coffee-specific diterpenes cafestol and kahweol (C + K) increased NQO1 mRNA up to 9-fold. MEFs from nrf2(-/-) mice expressed less NQO1 mRNA than did wild-type MEFs, but NQO1 was induced modestly by coffee or C + K in the mutant fibroblasts. Transfection of MEFs with nqo1-luciferase reporter constructs showed that induction by C + K was mediated primarily by Nrf2 and required the presence of an antioxidant response element in the 5'-upstream region of the gene. Luciferase reporter activity did not increase following treatment of MEFs with 100 mu mol/l furan, suggesting that this ring structure within C + K is insufficient for gene induction. Priming of nrf2(+/+) MEFs, but not nrf2(-/-) MEFs, with C + K conferred 2-fold resistance towards acrolein. (c) 2007 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)328-337
    Number of pages10
    JournalToxicology and Applied Pharmacology
    Volume226
    Issue number3
    DOIs
    Publication statusPublished - 1 Feb 2008

    Keywords

    • antioxidant response element
    • arylhydrocarbon receptor
    • glutathione S-transferase
    • NAD(P)H : quinone oxidoreductase 1
    • Nrf2
    • GLUTATHIONE-S-TRANSFERASE
    • ANTIOXIDANT RESPONSE ELEMENT
    • ARYL-HYDROCARBON RECEPTOR
    • GLUTAMATE-CYSTEINE LIGASE
    • INDUCIBLE EXPRESSION
    • CONSENSUS SEQUENCE
    • GENE-EXPRESSION
    • LEUCINE-ZIPPER
    • NAD(P)H-QUINONE OXIDOREDUCTASE-1
    • BUTYLATED HYDROXYANISOLE

    Cite this