Journal
PROTEIN JOURNAL
Volume 30, Issue 7, Pages 447-456Publisher
SPRINGER
DOI: 10.1007/s10930-011-9350-0
Keywords
CYP1A2; Inhibition; Isopimpinellin; Imperatorin; Trioxsalen
Categories
Funding
- Minnesota Agricultural Experiment Station
- National Cancer Institute [T32CA132670]
Ask authors/readers for more resources
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 mu M, 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 mu M, 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available