title: 4-Methylsulfanyl-3-butenyl isothiocyanate derived from glucoraphasatin is a potent inducer of rat hepatic phase II enzymes and a potential chemopreventive agent.
abstract: The objective of this study was to establish whether the phytochemical glucoraphasatin, a glucosinolate present in cruciferous vegetables, and its corresponding isothiocyanate, 4-methylsulfanyl-3-butenyl isothiocyanate, up-regulate enzymes involved in the detoxification of carcinogens and are thus potential chemopreventive agents. Glucoraphasatin and myrosinase were isolated and purified from Daikon sprouts and Sinapis alba L., respectively. Glucoraphasatin (0-10 μM) was incubated for 24 h with precision-cut rat liver slices in the presence and absence of myrosinase, the enzyme that converts the glucosinolate to the isothiocyanate. The intact glucosinolate failed to influence the O-dealkylations of methoxy- and ethoxyresorufin or the apoprotein expression of CYP1 enzymes. Supplementation with myrosinase led to an increase in the dealkylation of methoxyresorufin, but only at the highest concentration of the glucosinolate, and CYP1A2 expression. In the absence of myrosinase, glucoraphasatin caused a marked increase in epoxide hydrolase activity at concentrations as low as 1 μM paralleled by a rise in the enzyme protein expression; at the highest concentration only, a rise was also observed in glucuronosyl transferase activity, but other phase II enzyme systems were unaffected. Addition of myrosinase to the glucoraphasatin incubation maintained the rise in epoxide hydrolase and glucuronosyl transferase activities, further elevated quinone reductase and glutathione S-transferase activities, and increased total glutathione concentrations. It is concluded that at low concentrations, glucoraphasatin, either intact and/or through the formation of 4-methylsulfanyl-3-butenyl isothiocyanate, is a potent inducer of hepatic enzymes involved in the detoxification of chemical carcinogens and merits further investigation for chemopreventive activity.
authors.affiliation: Molecular Toxicology Group, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
authors.forename: Ahmed Faizal
authors.initials: AF
authors.lastname: Abdull Razis
authors.forename: Gina Rosalinda
authors.initials: GR
authors.lastname: De Nicola
authors.forename: Eleonora
authors.initials: E
authors.lastname: Pagnotta
authors.forename: Renato
authors.initials: R
authors.lastname: Iori
authors.forename: Costas
authors.initials: C
authors.lastname: Ioannides
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D019607:Brassicaceae / Q000737:chemistry*; D004790:Enzyme Induction / Q000187:drug effects; D005961:Glucosinolates / Q000737:chemistry* / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000378:metabolism; D008658:Inactivation, Metabolic; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008113:Liver Neoplasms / Q000188:drug therapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D031226:Sinapis / Q000737:chemistry
chemical_list: C507366:4-methylthio-3-butenyl glucosinolate; D016588:Anticarcinogenic Agents; D005961:Glucosinolates; D017879:Isothiocyanates; D010936:Plant Extracts; D006026:Glycoside Hydrolases; C022739:thioglucosidase