Induction of NADPH:quinone oxidoreductase in murine hepatoma cells by methylsulfinyl isothiocyanates: methyl chain length-activity study

Int J Mol Med. 2000 Oct;6(4):441-4. doi: 10.3892/ijmm.6.4.441.

Abstract

Methylsulfinyl isothiocyanates (MITC) are a class of isothiocyanates occurring in a variety of cruciferous vegetables showing anticarcinogenic activity. To develop analogues of methylsulfinyl isothiocyanate with less toxicity and better biological activity, four types of methyl chain length (designated as 2-, 4-, 6- and 8-MITC) were synthesized. The murine hepatoma cells (Hepa 1c1c7) were treated with various concentrations of MITC, and then assessed for cell growth, enzyme activity and mRNA expression of the detoxifying enzyme NADPH:quinone oxidoreductase (QR). All of four MITC augmented the induction of QR activity and the expression of QR mRNA in a dose-dependent manner. In the non-toxic concentration range, an increase in the methyl chain length resulted in a higher QR induction in both activity and mRNA expression. However, increasing cytotoxicity was also observed by an increase in the methyl chain length. Our results suggested that 4- and 6-MITC as QR inducers appeared to be less toxic and even more potent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / pathology
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Enzymologic
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology*
  • Mice
  • NAD(P)H Dehydrogenase (Quinone) / drug effects*
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Isothiocyanates
  • RNA, Messenger
  • NAD(P)H Dehydrogenase (Quinone)