title: Effects of furanocoumarins from apiaceous vegetables on the catalytic activity of recombinant human cytochrome P-450 1A2.
abstract: Inhibition of cytochrome P-450 1A2 (CYP1A2)-mediated activation of procarcinogens may be an important chemopreventive mechanism. Consumption of apiaceous vegetables (rich in furanocoumarins) inhibits CYP1A2 in humans. Because many furanocoumarins are potent inhibitors of several CYPs, we characterized the effects of three furanocoumarins from apiaceous vegetables on human CYP1A2 (hCYP1A2). We assessed hCYP1A2 methoxyresorufin O-demethylase (MROD) activity using microsomes from Saccharomyces cerevisiae expressing hCYP1A2. Isopimpinellin exhibited mechanism-based inactivation (MBI) of hCYP1A2 (K(i) = 1.2 μM, k (inact) = 0.34 min⁻¹, and partition ratio = 8). Imperatorin and trioxsalen were characterized as mixed inhibitors with K(i) values of 0.007 and 0.10 μM, respectively. These results indicate that even if present at low levels in apiaceous vegetables, imperatorin, trioxsalen and isopimpinellin may contribute significantly to CYP1A2 inhibition and potentially decreased procarcinogen activation. Moreover, the in vivo effect of isopimpinellin on CYP1A2 may be longer lasting compared to reversible inhibitors.
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, 225 Food Science and Nutrition, 1334 Eckles Avenue, St. Paul, MN, 55108-1038, USA.
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Kang
authors.forename: Lindsay R
authors.initials: LR
authors.lastname: Young
authors.forename: Carlus
authors.initials: C
authors.lastname: Dingfelder
authors.forename: Sabrina
authors.initials: S
authors.lastname: Peterson
mesh_terms: D055162:Biocatalysis / Q000187:drug effects; D019388:Cytochrome P-450 CYP1A2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014675:Vegetables / Q000737:chemistry*
chemical_list: D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004791:Enzyme Inhibitors; D011564:Furocoumarins; D010936:Plant Extracts; D011994:Recombinant Proteins; D019388:Cytochrome P-450 CYP1A2