6-methylsulfinylhexyl-isothiocyanate and Carcinoma--Hepatocellular

Wasabi is a very popular pungent spice in Japan. This study examined the ability of 6-(methylsufinyl)hexyl isothiocyanate (6-MITC), an active principle of wasabi, to induce the cellular expression of nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase (QR) in Hepa 1c1c7 cells. The cells were treated with various concentrations of 6-MITC, and were then assessed for cell growth, QR activity and QR mRNA expression. The induction of QR activity and QR mRNA expression was time- and dose-responsive over a narrow range of 0.1-5 microM, with declining induction at higher concentrations due to cell toxicity. Furthermore, transfection studies demonstrated that the induction of transcription of the QR gene by 6-MITC involved an antioxidant/electrophile-responsive element (ARE/EpRE) activation. Our results suggest a novel mechanism by which dietary wasabi 6-MITC may be implicated in cancer chemoprevention.

Topics: Animals; Antioxidants; Carcinoma, Hepatocellular; Dose-Response Relationship, Drug; Gene Expression Regulation; Glutathione Transferase; Humans; Isothiocyanates; Luciferases; Mice; Plasmids; Quinone Reductases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spices; Time Factors; Transcription, Genetic; Transcriptional Activation; Transfection; Tumor Cells, Cultured