Augmented gene expression of quinone reductase by 6-(methylsulfinyl)hexyl isothiocyanate through avoiding its cytotoxicity.
We examined both the induction of quinone reductase (QR) by 6-(methylsulfinyl)hexyl isothiocyanate and its cytotoxicity in Hepa1c1c7 cells, and compared the sensitivity of these two responses to NAC. QR activity was increased by 6-(methylsulfinyl)hexyl isothiocyanate in a dose-dependent manner. At 80 microM, the compound was significantly toxic to cells, but the resulting QR inhibition was dose-dependently overcome by NAC. Augmentation of QR activity by 6-(methylsulfinyl)hexyl isothiocyanate seemed to be due to augmented expression of QR mRNA, which was significantly increased by the compound. Inhibition of QR gene expression was seen at 80 microM and could be overcome by NAC. Optimal induction of QR gene expression by the compound (at 40 microM) was slightly but significantly inhibited by 10 mM NAC but not by 1 mM. The present study suggests that induction of Phase 2 detoxification enzymes by isothiocyanate compounds may be further enhanced by suppression of their inherent cytotoxic activity.
Ryoyama
Kazuo
K
Department of Bioscience and Biotechnology, Faculty of Engineering, Aomori University, Aomori 030-0943, Japan. ryoyama@aomori-u.ac.jp
Mori
Naoto
N
Nara
Motoki
M
Kidachi
Yumi
Y
Yamaguchi
Hideaki
H
Umetsu
Hironori
H
Fuke
Yoko
Y
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017879:Isothiocyanates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis* / Q000235:genetics
C111984:6-methylsulfinylhexyl isothiocyanate; D017879:Isothiocyanates; D016660:NAD(P)H Dehydrogenase (Quinone); D000111:Acetylcysteine