Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/27/2006
Publication Date: 5/1/2007
Citation: Mikstacka, R., Przybylska, D., Rimando, A.M., Baer-Dubowska, W. 2007. Inhibition of Human Recombinant Cytochromes P450 CYP1A1 and CYP1B1 by Trans-resveratrol Methyl Ethers. Molecular Nutrition and Food Research. 51(5):517-524. Interpretive Summary: Studies were conducted to determine the inhibitory effect of the naturally-occurring phenolic compounds pinostilbene, desoxyrhapontigenin, and pterostilbene against the enzyme cytochrome P450 subtypes 1A1 and 1B1. These enzymes are responsible for the transformation of some procarcinogens (e.g., polycyclic aromatic hydrocarbons, heterocyclic amines and estradiol) to the carcinogenic intermediates. These analogs of trans-resveratrol appeared to be very potent inhibitors of CYP1A1, more potent than resveratrol. However, the inhibitory effect on CYP1B1 was comparable to that of resveratrol. 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 having been shown to effectively modulate the activities of CYP1A1 and CYP1B1.
Technical Abstract: CYP 1A1 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 1B1. 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 µM, 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 CYP 1A1 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, 0.91 µM, 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 having been shown to effectively modulate CYP1A1 and CYP1B1 activities.