Effects of coffee and its chemopreventive components kahweol and cafestol on cytochrome P450 and sulfotransferase in rat liver

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 ∼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 ∼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.