| 18028974 |
Higgins LG, Cavin C, Itoh K, Yamamoto M, Hayes JD: Induction of cancer chemopreventive enzymes by coffee is mediated by transcription factor Nrf2. Toxicol Appl Pharmacol. 2008 Feb 1;226(3):328-37. Epub 2007 Sep 26.
Evidence that the coffee-specific diterpenes cafestol and kahweol confer protection against acrolein.. 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 mumol/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. |
1(0,0,0,1) |