Furanocoumarins from apiaceous vegetables inhibit human cytochrome P‐450 1A2 activity

Cytochrome P‐450 1A2 (CYP1A2) activates several procarcinogens. Apiaceous vegetables contain furanocoumarins and it has been suggested that the furanocoumarins are responsible for in vivo inhibition of CYP1A2. Investigations thus far have only focused on the predominant furanocoumarins in apiaceous vegetables. Hence, we tested four furanocoumarins present in lower amounts in apiaceous vegetables for effects on human CYP1A2 activity (methoxyresorufin O‐demethylation or MROD) using microsomes from yeast expressing human CYP1A2. Imperatorin, trioxsalen, isopimpinellin, and angelicin all potently inhibited CYP1A2‐mediated MROD activity with IC 50 values of 0.02 μM, 0.12 μM, 0.39μM, and 9.7 μM, respectively. All but angelicin were at least 4–75 times more potent than previously studied furanocoumarins in apiaceous vegetables. These results indicate that despite their low levels in apiaceous vegetables, imperatorin, trioxsalen and isopimpinellin may contribute significantly to CYP1A2 inhibition in vivo. The inhibitory effects of apiaceous vegetables on CYP1A2 may be chemopreventive, however, the inhibition mechanism and anti‐mutagenesis effects of these furanocoumarins still need to be studied.