title: Inhibition of cytochrome P450 2C9 expression and activity in vitro by allyl isothiocyanate.
abstract: The growing interest in the use of natural herbal products and dietary supplements to treat and prevent diseases raises the question of medicinal drug safety. Allyl isothiocyanate, a hydrolysis product of a glucosinolate, sinigrin, has multiple beneficial properties, and based on this fact, allyl isothiocyanate-containing dietary supplements have been developed. To date, no studies of the effects of this compound on the cytochrome P450 2C9 have been reported. In this study, we found that allyl isothiocyanate reduced catalytic activity, messenger ribonucleic acid, and protein expression of cytochrome P450 2C9 in HepaRG cells. An investigation of the transcriptional activity of the pregnane X receptor and the constitutive androstane receptor revealed that allyl isothiocyanate disrupted the transcriptional coregulation effects of the pregnane X receptor/constitutive androstane receptor with several important coregulators and interfered with the assembly of transcriptional complexes of the cytochrome P450 2C9 pregnane X receptor/constitutive androstane receptor-response element. The decrease of cytochrome P450 2C9 expression and activity mediated by allyl isothiocyanate suggested that this agent could alter the metabolism of drugs metabolized by cytochrome P450 2C9. This may cause food/dietary supplement-drug interactions or alter the therapeutic effects, and even the toxicity of drugs coadministered with allyl isothiocyanate. Since the consumption of allyl isothiocyanate-containing food/dietary supplements continues to increase, it is important to predict and ultimately avoid interactions with concomitant drugs. It is required that these possible pharmacokinetic interactions be characterized and the recommendations available to patients and healthcare professionals be improved.
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Lim
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Ching-Hao
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Yu-Hsien
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Cing-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Dong-Zong
authors.initials: DZ
authors.lastname: Hung
authors.affiliation: Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung, Taiwan, ROC.
authors.forename: Jih-Jung
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yokoi
authors.affiliation: Department of Pharmacy, Changhua Show Chwan Memorial Hospital, Changhua, Taiwan, ROC.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Chao-Jung
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D000090702:Constitutive Androstane Receptor; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism*; D065688:Cytochrome P-450 CYP2C9 Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism
chemical_list: D000090702:Constitutive Androstane Receptor; D065688:Cytochrome P-450 CYP2C9 Inhibitors; D017879:Isothiocyanates; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; C004471:allyl isothiocyanate; D065729:Cytochrome P-450 CYP2C9