Phenethyl isothiocyanate, a naturally occurring phytochemical, is an antagonist of the aryl hydrocarbon receptor

• Published in: Molecular nutrition & food research Vol. 56; no. 3; pp. 425 - 434
• Main Authors: Abdull Razis, Ahmad F., Konsue, Nattaya, Dervetzoglou, Myrto, Plant, Kathryn E., Plant, Nick, Ioannides, Costas
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.03.2012; WILEY‐VCH Verlag; Wiley
• Subjects: Aged; Ah receptor; Animals; Benzo(a)pyrene - toxicity; Biological and medical sciences; Carcinogens - toxicity; Cells, Cultured; Chemoprevention; Cruciferous vegetables; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1A1 - metabolism; Female; Food industries; Fruit and vegetable industries; Fundamental and applied biological sciences. Psychology; Glucosinolates; Humans; Isothiocyanates - pharmacology; Liver - drug effects; Liver - metabolism; Male; Middle Aged; Oxazines - metabolism; Phenethyl isothiocyanate; Rats; Rats, Wistar; Receptors, Aryl Hydrocarbon - antagonists & inhibitors; Receptors, Aryl Hydrocarbon - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Vegetables - chemistry; Sulfur compounds; Ah receptor; Cruciferous vegetables; Phenethyl isothiocyanate; Glucosinolate; Vegetables; Hydrocarbon; Chemoprevention; Glucosinolates; Antagonist; Isothiocyanates
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201100548

Scope The aryl hydrocarbon (Ah) receptor is a ligand‐activated transcription factor that is activated by many carcinogens, and its target gene products play a major role in tumour development, so that antagonists of the Ah receptor represent potential chemopreventive agents. Methods and results Experimental evidence is presented herein that phenethyl isothiocyanate (PEITC), a phytochemical present in cruciferous vegetables, is such an antagonist. PEITC was a very weak ligand to the Ah receptor, as assessed using the chemical‐activated luciferase expression (CALUX) assay, and a poor inducer of CYP1A1 mRNA levels when incubated in precision‐cut rat liver slices for 24 h. It antagonised effectively, however, the interaction of benzo[a]pyrene to the receptor, being capable of preventing its binding as well as displacing it from the receptor. Moreover, PEITC suppressed in concentration‐dependent manner the benzo[a]pyrene‐mediated rise in rat hepatic CYP1A1 mRNA levels in rat slices. Finally, PEITC antagonised the benzo[a]pyrene‐mediated increase in the O‐deethylation of ethoxyresorufin in both rat and human precision‐cut liver slices. Conclusion It is concluded that PEITC is an effective antagonist of the Ah receptor in rat and human liver, and this potential may contribute to its established chemopreventive activity.