• BMB Reports
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• v.32 no.2
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• pp.127-132
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• 1999

The NAD(P)H-quinone oxidoreductase (EC 1. 6. 99. 2) was purified from S. cerevisiae. The native molecular weight of the enzyme is approximately 111 kDa and is composed of five identical subunits with molecular weights of 22 kDa each. The optimum pH of the enzyme is pH 6.0 with 1,4-benzoquinone as a substrate. The apparent $k_m$ for 1,4-benzoquinone and 1,4- naphthoquinone are 1.3 mM and $14.3\;{\mu}M$, respectively. Its activity is greatly inhibited by $Cu^{2+}$ and $Hg^{2+}$ ions, nitrofurantoin, dicumarol, and Cibacron blue 3GA. The purified NAD(P)H-quinone oxidoreductase was found capable of reducing aromatic nitroso compounds as well as a variety of quinones, and can utilize either NADH or NADPH as a source of reducing equivalents. The nitroso reductase activity of the purified NAD(P)H-quinone oxidoreductase is strongly inhibited by dicumarol.

• Natural Product Sciences
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• v.7 no.2
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• pp.38-44
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• 2001

NAD(P)H:quinone reductase (QR), known as DT-diaphorase, is a kind of detoxifying phase II metabolic enzyme catalyzing hydroquinone formation by two electron reduction pathway from quinone type compounds, and thus facilitating excretion of quinoids from human body. With the usefulness of QR induction activity assay system for the modulation of toxicants, in the course of searching for cancer chemopreventive agents from natural products, the methanolic extracts of approximately two hundreds of oriental medicines were primarily evaluated using the induction potential of quinone reductase (QR) activity in cultured murine Hepa1c1c7 cells. As a result, several extracts including Hordeum vulgare, Momordica cochinchinensis, Strychnos ignatii, Houttuynia cordata, and Polygala japonica were found to significantly induce QR activity. In addition, the methylene chloride fraction of H. vulgare, one major dietary food source, showed potent induction of QR activity $(CD=6.4{\mu}g/ml)$. Further study for isolation of active principles from these lead extracts is warranted for the discovery of novel cancer chemopreventive agents.

• Natural Product Sciences
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• v.3 no.2
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• pp.81-88
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• 1997

NAD(P)H:quinone reductase (QR) is one of the protective phase II enzymes against toxicity that accomplishes the capacity of detoxification by modulating the effects of mutagens and carcinogens. The detoxification mechanism is that quinone reductase promotes the 2-electron reduction of quinones to hydroquinones which are less reactive. This study is to search new inducers of quinone reductase from natural products, which can be used as cancer chemopreventive agents. Plant extracts were evaluated by using quinone reductase generating system With Hepa 1c1c7 murine hepatoma cell lines for enzyme inducing properties and crystal violet staining method for the measurement of cytotoxicity provoked. We have tested approximately 106 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from 100% methanol extracts of natural products. The ethyl acetate fractions of Vitex rotundifolia $(fruits,\;2FC:\;12.7\;{\mu}g/ml)$, Cnidium officinale $(aerial\;parts,\;2FC:\;10.5\;{\mu}g/ml)$, Chrysanthemum sinese $(flowers,\;2FC:\;17.4{\mu}g/ml)$ and the hexane fractions of Angelica gigas $(roots,\;2FC:\;13.2\;{\mu}g/ml)$, Smilax china $(roots,\;2FC:\;l1.9\;{\mu}g/ml)$, Sophora flavescens $(roots,\;2FC:\;16.3\;{\mu}g/ml)$ revealed the significant induction of quinone reductase in a murine hepatic Hepa 1c1c7 cell culture system.

• Korean Journal of Pharmacognosy
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• v.32 no.4 s.127
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• pp.269-273
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• 2001

Ethanol extracts from Xanthii Fructus (XFE) and Prunellae Spica (PSE) were investigated for the effects on the induction of cancer chemoprevention-associated enzymes. The following effects were measured: (a) induction of quinone reductase (QR) (b) induction of glutathione S-transferase (GST) (c) reduced glutathione (GSH) level. XFE and PSE were potent inducers of quinone reductase activity in Hepa1c1c7 murine hepatoma cells. Glutathione levels were increased with XFE and PSE. In addition, glutathione S-transferase activity was increased with XFE. However, GST activity was not increased with PSE. These results suggest that XFE and PSE have chemopreventive potentials by inducing quinone reductase and increasing GSH levels.

• Korean Journal of Food Science and Technology
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• v.27 no.6
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• pp.972-977
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• 1995

The induction of phase II enzymes including quinone reductase [NAD(P)H dehydrogenase(quinone): NAD(P)H : (quinone acceptor) oxidoreductase, EC 1.6.99.2] is a major mechanism of whereby a large group of heterogeneous compounds prevent the toxic, mutagenic, and neoplastic effects of carcinogen. Using murine hepatoma cells(Hepalclc7 cells), quinone reductase(QR) inducers as the possible chemopreventive agents were screened from rice bran, wheat bran, soymilk residue, defatted soybean cake, defatted sesame and perilla residues. The 80% methanol extracts of defatted sesame and perilla residues induced quinone reductase significantly while the others did have little effect on the enzyme induction. Thin layer chromatography of the extracts showed that the fastest moving band(Rf=0.70) in the developing solvent of n-butanol : n-propanol : 2N ammonia(10 : 60 : 30) was responsible for the enzyme induction by the 80% methanol extracts of defatted sesame and perilla residues. Further identification of active component(s) is in progress.

• 한국생물공학회:학술대회논문집
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• 2000.11a
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• pp.638-639
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• 2000

Quinone reductase was purified to electrophoretic homogeneity from bovine liver by using ammonium sulfate fractionation, ion-exchange chromatography, and gel filtration chromatography. The enzyme utilized either NADH or NADPH as the electron donor. The optimum pH of the enzyme was pH 8.5, and the activity of the enzyme was greatly inhibited by $Cu^{2+}$ and $Hg^{2+}$ ions, dicumarol and cibacron blue 3GA. The enzyme catalyzed the reduction of several quinones and other artificial electron acceptors. Furthermore, the enzyme catalyzed NAD(P)H-dependent reduction of azobenzene or 4-nitroso-N,N-dimethylaniline. The apparent $K_m$ for 1,4-benzoquinone, azobenzene, and 4-nitroso-N,N-dimethylaniline was 1.64mM, 0.524mM and 0.225mM, respectively. The reduction of azobenzene or 4-nitroso-N,N-dimethylaniline by quinone reductase was strongly inhibited by dicumarol or cibacron blue 3GA, potent inhibitors of quinone reductase.

• BMB Reports
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• v.33 no.4
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• pp.321-325
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• 2000

Quinone reductase was purified to homogeneity from bovine liver by using ammonium sulfate fractionation, ionexchange chromatography, and gel filtration chromatography. The enzyme utilized either NADH or NADPH as the electron donor. The enzyme catalyzed the reduction of several quinones and other artificial electron acceptors. Furthermore, the enzyme catalyzed NAD(P)H-dependent reduction of azobenzene. The apparent Km for 1,4-benzoquinone and azobenzene was 1.64 mM and 0.524 mM, respectively. The reduction of azobenzene by quinone reductase was almost entirely inhibited by dicumarol or Cibacron blue 3GA, potent inhibitors of the mammalian quinone reductase. In the presence of 1.0${\mu}M$ Cibacron blue 3GA, azoreductase activity was lowered by 45%, and almost complete inhibition was seen above 2.0 ${\mu}M$ Cibacron blue 3GA.

• Korean Journal of Acupuncture
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• v.18 no.1
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• pp.21-26
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• 2001

Induction of phase II enzymes such as quinone reductase (QR) or glutathione S-transferase (GST) is considered a major mechanism of protection against initiation of carcingenesis. This study was desinged to investigate the potential of Astragali Radix Aqua-acupuncture Solution (ARAS) to induce phase II enzymes and glutathione (GSH) in murine hepatoma cells grown in microtiter plate wells. ARAS was potent inducers of QR activity. ARAS was induced about 2.6-fold at concentration of $5{\times}$. In addition, GST activity was increased with ARAS. GSH levels were increased about 1.2-fold with ARAS at concentration of $0.1{\times}$. These results suggested that ARAS may act as blocking agents against carcinogenesis by induction of phase II marker enzymes.

• Preventive Nutrition and Food Science
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• v.4 no.2
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• pp.122-124
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• 1999

Induction of NAD(P)H : (quinone-acceptor) oxidoreductase (QR) which obligatory two electron reduction of quinones and prevents their participation in oxidative cycling and thereby the depletion of intracellular glutathione, has been used as a marker for chemopreventive agents. We postulated that vitamin E, an antioxidant, which induces QR as the gene of QR was reported to contain antioxidant reponsive element in the 5'-flanking region. Vitamin E resulted in significant induction of QR in both hepalclc7 cells and mouse tissues. QR induction was observed; to be maximal at 25uM vitamin E for hepalclc7 cells while it was maximal in the level of 2.5∼5 μmoles vitamin E/㎏ BW for mouse tissues. Thus the cancer-preventive effect of vitamin E may be exerted by it induction of intracellular detoxifying enzymes.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.161.1-161.1
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• 2003

NAD(P)H:quinone oxidoreductase (quinone reductase: QR: EC1.6.99.2), a cytosolic FAD-containing flavoprotein, form one of the important component of the phase II drug-metabolizing enzyme systems. It is found in all mammalian species tested and is expressed in many organs including the liver. QR catalyses two-electron reduction of qui nones to hydroquinones thereby suppresses the formation of superoxide anion radical. (omitted)