Inhibition of human recombinant cytochromes P450 CYP1A1 and CYP1B1 by trans-resveratrol methyl ethers.
CYP1A1 and CYP1B1 are the inducible forms of cytochrome P450 expressed in extrahepatic tissues, which are responsible for the biotransformation of polycyclic aromatic hydrocarbons, heterocyclic amines and estradiol to the carcinogenic intermediates. The aim of our research was to determine and compare the inhibitory effect of naturally occurring analogues of trans-resveratrol on the catalytic activities of human recombinant CYP1A1 and CYP1B1. Pinostilbene (3,4'-dihydroxy-5-methoxystilbene), desoxyrhapontigenin (3,5-dihydroxy-4'-methoxystilbene), and pterostilbene (3,5-dimethoxy-4'-hydroxystilbene) appeared to be very potent inhibitors of CYP1A1 catalytic activity with Ki values of 0.13, 0.16 and 0.57 microM, respectively. Results from this study indicate that trans-resveratrol analogues in which the hydroxy groups are substituted by methoxy groups exhibit a remarkably stronger inhibitory effect towards CYP1A1 in comparison to the parent compound. On the contrary, the potency of pinostilbene, desoxyrhapontigenin and pterostilbene towards CYP1B1 with Ki values of 0.90, 2.06 and 0.91 microM, respectively, was comparable to that of resveratrol. It appears that between these analogues, inhibition of CYP1A1 and CYP1B1 catalytic activities does not vary much regardless of the number and position of methylether substitution. The results suggest that the trans-resveratrol analogues: pinostilbene, desoxyrhapontigenin and pterostilbene, which occur in some food plants, might be considered as promising chemopreventive agents.
Mikstacka
Renata
R
Department of Pharmaceutical Biochemistry, University of Medical Sciences, Poznan, Poland. rmikstac@amp.edu.pl
Przybylska
Dorota
D
Rimando
Agnes M
AM
Baer-Dubowska
Wanda
W
D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors*; D065633:Cytochrome P-450 CYP1B1; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008738:Methyl Ethers / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
C439024:3,5-dihydroxy-4'-methoxystilbene; D004791:Enzyme Inhibitors; D008738:Methyl Ethers; D011994:Recombinant Proteins; D013267:Stilbenes; C522997:pinostilbene; C107773:pterostilbene; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D000077185:Resveratrol