title: Effects of coffee and its chemopreventive components kahweol and cafestol on cytochrome P450 and sulfotransferase in rat liver.
abstract: Coffee drinking appears to reduce cancer risk in liver and colon. Such chemoprevention may be caused by the diterpenes kahweol and cafestol (K/C) contained in unfiltered beverage. In animals, K/C treatment inhibited the mutagenicity/tumorigenicity of several carcinogens, likely explicable by beneficial modifications of xenobiotic metabolism, particularly by stimulation of carcinogen-detoxifying phase II mechanisms. In the present study, we investigated the influence of K/C on potentially carcinogen-activating hepatic cytochrome P450 (CYP450) and sulfotransferase (SULT). Male F344 rats received 0.2% K/C (1:1) in the diet for 10 days or unfiltered and/or filtered coffee as drinking fluid. Consequently, K/C decreased the metabolism of four resorufin derivatives representing CYP1A1, CYP1A2, CYP2B1, and CYP2B2 activities by approximately 50%. For CYP1A2, inhibition was confirmed at the mRNA level, accompanied by decreased CYP3A9. In contrast to K/C, coffee increased the metabolism of the resorufin derivatives up to 7-fold which was only marginally influenced by filtering. CYP2E1 activity and mRNA remained unchanged by K/C and coffee. K/C but not coffee decreased SULT by approximately 25%. In summary, K/C inhibited CYP450s by tendency but not universally. Inhibition of CYP450 and SULT may contribute to chemoprevention with K/C but involvement in the protection of coffee drinkers is unlikely. The data confirm that the effects of complex mixtures may deviate from those of their putatively active components.
authors.affiliation: Research Unit of Toxicology and Prevention, Division Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8A, A-1090 Vienna, Austria. wolfgang.huber@meduniwien.ac.at <wolfgang.huber@meduniwien.ac.at>
authors.forename: Wolfgang W
authors.initials: WW
authors.lastname: Huber
authors.forename: Walter
authors.initials: W
authors.lastname: Rossmanith
authors.forename: Michael
authors.initials: M
authors.lastname: Grusch
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Haslinger
authors.forename: Sonja
authors.initials: S
authors.lastname: Prustomersky
authors.forename: Barbara
authors.initials: B
authors.lastname: Peter-Vörösmarty
authors.forename: Wolfram
authors.initials: W
authors.lastname: Parzefall
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Scharf
authors.forename: Rolf
authors.initials: R
authors.lastname: Schulte-Hermann
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015239:Arylsulfotransferase / Q000378:metabolism*; D003069:Coffee / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D005374:Filtration; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D023282:Nuclease Protection Assays; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D016588:Anticarcinogenic Agents; D003069:Coffee; D004224:Diterpenes; D007527:Isoenzymes; D012313:RNA; C053401:kahweol; D003577:Cytochrome P-450 Enzyme System; C053400:cafestol; D015239:Arylsulfotransferase