Health & Environmental Research Online (HERO)


Print Feedback Export to File
2123374 
Journal Article 
Review 
Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity 
Cavin, C; Holzhaeuser, D; Scharf, G; Constable, A; Huber, WW; Schilter, B 
2002 
Yes 
Food and Chemical Toxicology
ISSN: 0278-6915
EISSN: 1873-6351 
PERGAMON-ELSEVIER SCIENCE LTD 
OXFORD 
40 
8 
1155-1163 
English 
12067578 
WOS:000177393700016 
Epidemiological studies have found an inverse association between coffee consumption and the risk of certain types of cancers such as colorectal cancers. Animal data support such a chemopreventive effect of coffee. Substantial research has been devoted to the identification of coffee components that may be responsible for these beneficial effects. In animal models and cell culture systems, the coffee diterpenes cafestol and kahweol (C+K) were shown to produce a broad range of biochemical effects resulting in a reduction of the genotoxicity of several carcinogens including 7,12-dimethylbenz[a]anthracene (DMBA), aflatoxin B-1 (AFB(1)), benzo[a]pyrene (B[a]P) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Different mechanisms appear to be involved in these chemoprotective effects: an induction of conjugating enzymes (e.g. glutathione S-transferases, glucuronosyl S-transferases), an increased expression of proteins involved in cellular antioxidant defense (e.g. gamma-glutamyl cysteine synthetase and heme oxygenase-1) and an inhibition of the expression and/or activity of cytochromes P450 involved in carcinogen activation (e.g. CYP2C11, CYP3A2). In animal models, the C+K-mediated induction of conjugating and antioxidant enzymes has been observed in hepatic, intestinal and kidney tissues. In the small intestine, these inductions were shown to be mediated by Nrf2-dependent transcriptional activation. In vitro investigations obtained in cell cultures of human origin indicate that the effects and mechanisms observed in animal test systems with C+K are likely to be of relevance for humans. In human liver epithelial cell lines transfected to express AFB1-activating P450s, C+K treatment resulted in a reduction of AFB(1)-DNA binding. This protection was correlated with an induction of GST-mu, an enzyme known to be involved in AFB, detoxification. In addition, C+K was found to inhibit P450 2136, one of the human enzymes responsible for AFB(1) activation. Altogether, the data on the biological effects of C+K provide a plausible hypothesis to explain some of the anticarcinogenic effects of coffee observed in human epidemiological studies and in animal experiments. (C) 2002 Elsevier Science Ltd. All rights reserved. 
cafestol and kahweol; coffee; diterpenes; chemoprotection; mechanisms; blocking agents; glutathione S-transferases; cytochromes p450 
International Conference on Dietary Factors 
VIENNA, AUSTRIA