Nuclear Factor E2-Related Factor 2-Mediated Induction of NAD(P)H:Quinone Oxidoreductase 1 by 3,5-Dimethoxy-trans-stilbene

College of Pharmacy, Ewha Womans University, Seoul, Korea.
Journal of Pharmacological Sciences (Impact Factor: 2.36). 05/2011; 116(1):89-96. DOI: 10.1254/jphs.11024FP
Source: PubMed


NAD(P)H:quinone oxidoreductase 1 (NQO1), a phase II enzyme, plays an important role in the detoxification or chemoprotection of carcinogens, and induction of this enzyme is a target for the prevention of carcinogenesis. Natural stilbenoids have potential cancer chemopreventive activities, potentially through affecting NQO1 activity. Along this line, several stilbenoids were evaluated to procure more potent compounds for inducing NQO1 activity in cultured murine Hepa 1c1c7 cells. As a result, we found that 3,5-dimethoxy-trans-stilbene (DMS) possesses potent NQO1 induction activity through up-regulation of both protein and mRNA expression of NQO1 as determined by Western blot and reverse transcription-polymerase chain reaction analysis, respectively. DMS also increased protein expression of heme oxygenase-1 (HO-1), another phase II enzyme. This induction of NQO1 and HO-1 by DMS was closely related to the regulation of nuclear factor E2-related factor 2 (Nrf2). The translocation and activation of Nrf2 by DMS was also involved in the modulation of the upstream signal transduction molecule, protein kinase C δ. These findings suggest that DMS might have a cancer chemopreventive activity by inducing detoxifying enzymes such as NQO1 and HO-1.

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    • "FIG 3 BioFactors NADPH-cytochrome P450 reductase that generates semiquinone radicals that otherwise may either damage proteins and DNA or interact with O 2 to produce ROS-dependent oxidative stress [26]. Induction of NQO1 is a target for the prevention of carcinogenesis [29] or development of emphysema by oxidants in the lung [30]. In addition to Eh1 and NQO1, phase II detoxification enzymes also include GSTs, which catalyze the conjugation of xenobiotics containing electrophilic carbon, oxygen, nitrogen, or sulfur atoms with reduced glutathione (GSH), either with electrophilic agents as such or produced by phase I biotransformation (Fig. 4), which otherwise may bind to proteins inducing toxicity [26]. "
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