The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B1

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1: Carcinogenesis. 1998 Aug;19(8):1369-75.

The coffee-specific diterpenes cafestol and kahweol protect against

aflatoxin B1-induced genotoxicity through a dual mechanism.

Cavin C, Holzhauser D, Constable A, Huggett AC, Schilter B.

Nestle Research Center, Lausanne, Switzerland.

The diterpenes cafestol and kahweol (C & K) have been identified in

animal models as two potentially chemoprotective agents present in

green and roasted coffee beans. It has been postulated that these

compounds may act as blocking agents by producing a co-ordinated

modulation of multiple enzymes involved in carcinogen

detoxification. In this study, we investigated the effects of C & K

against the covalent binding of aflatoxin B1 (AFB1) metabolites to

DNA. Male Sprague-Dawley rats were treated with increasing amounts

of a mixture of C & K in the diet (0-6200 p.p.m.) for 28 and 90 days.

A dose-dependent inhibition of AFB1 DNA-binding was observed using

S9 and microsomal subcellular fractions from C & K-treated rat liver

in an in vitro binding assay. Significant inhibition was detected at

2300 p.p.m. and maximal reduction of DNA adduct formation to nearly

50% of the control value was achieved with 6200 p.p.m. of dietary

C & K. Two complementary mechanisms may account for the

chemopreventive action of cafestol and kahweol against aflatoxin B1

in rats. A decrease in the expression of the rat activating

cytochrome P450s (CYP2C11 and CYP3A2) was observed, as well as a

strong induction of the expression of the glutathione-S-transferase

(GST) subunit GST Yc2, which is known to detoxify highly the most

genotoxic metabolite of AFB1. These data and the previously

demonstrated effects of C & K against the development of 7,12-

dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis at various

tissue sites suggest the potential widespread effect of these coffee

components against chemical carcinogenesis.

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