Effects of Furanocoumarins from Apiaceous Vegetabl

Authors: AhYoung Kang Lindsay R Young Carlus Dingfelder Sabrina Peterson

Publish Date: 2011/08/17

Volume: 30, Issue: 7, Pages: 447-456

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Abstract

Inhibition of cytochrome P450 1A2 CYP1A2mediated 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 Odemethylase MROD activity using microsomes from Saccharomyces cerevisiae expressing hCYP1A2 Isopimpinellin exhibited mechanismbased inactivation MBI of hCYP1A2 K i  = 12 μM k inact = 034 min−1 and partition ratio = 8 Imperatorin and trioxsalen were characterized as mixed inhibitors with K i values of 0007 and 010 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 inhibitorsThe authors gratefully acknowledge and thank Dr Patrick Hanna Department of Medicinal Chemistry University of Minnesota and Dr Linda von Weymarn Masonic Cancer Center University of Minnesota for their expert guidance The authors also thank Li Liu for assistance with development of assays This work has been supported in part by the Minnesota Agricultural Experiment Station and by Award Number T32CA132670 from the National Cancer Institute The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health

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