Transcriptional regulation of nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase in murine hepatoma cells by 6-(methylsufinyl)hexyl isothiocyanate, an active principle of wasabi (Eutrema wasabi Maxim)

Cancer Lett. 2000 Dec 20;161(2):195-200. doi: 10.1016/s0304-3835(00)00611-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / prevention & control
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation*
  • Glutathione Transferase / metabolism
  • Humans
  • Isothiocyanates / pharmacology
  • Luciferases / metabolism
  • Mice
  • Plasmids / metabolism
  • Quinone Reductases / biosynthesis*
  • Quinone Reductases / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spices
  • Time Factors
  • Transcription, Genetic*
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured

Substances

  • 6-methylsulfinylhexyl isothiocyanate
  • Antioxidants
  • Isothiocyanates
  • RNA, Messenger
  • Luciferases
  • NADH dehydrogenase (quinone)
  • Quinone Reductases
  • Glutathione Transferase