Effects of Coffee and Its Chemopreventive Components Kahweol and Cafestol on Cytochrome P450 and Sulfotransferase in Rat Liver

Food Chem Toxicol. 2008 Apr;46(4):1230-8. doi: 10.1016/j.fct.2007.09.094. Epub 2007 Sep 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Arylsulfotransferase / metabolism*
  • Coffee / chemistry*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Diterpenes / pharmacology*
  • Filtration
  • Isoenzymes / metabolism
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Nuclease Protection Assays
  • RNA / biosynthesis
  • Rats
  • Rats, Inbred F344

Substances

  • Anticarcinogenic Agents
  • Coffee
  • Diterpenes
  • Isoenzymes
  • RNA
  • kahweol
  • Cytochrome P-450 Enzyme System
  • cafestol
  • Arylsulfotransferase