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

    85 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

    @article{a3e401ffeaef4457b317d3dc9787b8d4,
    title = "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",
    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.",
    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",
    author = "Higgins, {Larry G.} and Christophe Cavin and Ken Toh and Masayuki Yamamoto and Hayes, {John D.}",
    year = "2008",
    month = "2",
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    language = "English",
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    }

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

    In: Toxicology and Applied Pharmacology, Vol. 226, No. 3, 01.02.2008, p. 328-337.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - 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

    AU - Higgins, Larry G.

    AU - Cavin, Christophe

    AU - Toh, Ken

    AU - Yamamoto, Masayuki

    AU - Hayes, John D.

    PY - 2008/2/1

    Y1 - 2008/2/1

    N2 - 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.

    AB - 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.

    KW - antioxidant response element

    KW - arylhydrocarbon receptor

    KW - glutathione S-transferase

    KW - NAD(P)H : quinone oxidoreductase 1

    KW - Nrf2

    KW - GLUTATHIONE-S-TRANSFERASE

    KW - ANTIOXIDANT RESPONSE ELEMENT

    KW - ARYL-HYDROCARBON RECEPTOR

    KW - GLUTAMATE-CYSTEINE LIGASE

    KW - INDUCIBLE EXPRESSION

    KW - CONSENSUS SEQUENCE

    KW - GENE-EXPRESSION

    KW - LEUCINE-ZIPPER

    KW - NAD(P)H-QUINONE OXIDOREDUCTASE-1

    KW - BUTYLATED HYDROXYANISOLE

    U2 - 10.1016/j.taap.2007.09.018

    DO - 10.1016/j.taap.2007.09.018

    M3 - Article

    VL - 226

    SP - 328

    EP - 337

    JO - Toxicology and Applied Pharmacology

    JF - Toxicology and Applied Pharmacology

    SN - 0041-008X

    IS - 3

    ER -