Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.5.2 (NQO1)
6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological and laboratory studies suggest that dietary broccoli may prevent or delay a variety of cancers. Broccoli and other crucifers contain a relatively unique family of secondary metabolites called glucosinolates. Glucoraphanin, the major glucosinolate in broccoli, is hydrolyzed by an endogenous plant myrosinase to form either the potent anticarcinogen sulforaphane (SF) or sulforaphane nitrile (SF nitrile). The bioactivities of SF and SF nitrile were compared in rats and in mouse hepatoma cells. Male, 4-week-old, Fischer 344 rats were administered SF or SF nitrile (200, 500, or 1000 micromol/kg) by gavage daily for 5 days. Hepatic, colonic mucosal, and pancreatic quinone reductase and glutathione S-transferase activities were induced by high doses of SF, but not by SF nitrile. When Hepa 1c1c7 cells were exposed to increasing levels of each compound for 24 h, quinone reductase showed a 3-fold maximal induction over control at 2.5 microM SF and a 3.5-fold maximal induction over control at 2000 microM SF nitrile, the highest concentration tested. These results demonstrate that SF nitrile is substantially less potent than SF as an inducing agent of phase II detoxification enzymes. Therefore, glucoraphanin hydrolysis directed toward the production of SF rather than SF nitrile could increase the potential chemoprotective effects of broccoli.
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PMID:Comparison of the bioactivity of two glucoraphanin hydrolysis products found in broccoli, sulforaphane and sulforaphane nitrile. 1174 57

Many dietary isothiocyanates (ITCs) have shown cancer chemoprotective activity in animal models. Isothiocyanates rapidly accumulate in cells of various types as glutathione conjugates, and the total intracellular accumulation levels of ITCs (area under time-concentration curve; AUC) were critical for their Phase 2 enzyme inducer activities in murine hepatoma Hepa 1c1c7 cells. Induction of Phase 2 detoxification enzymes is recognized as a major cellular defense against carcinogens and other toxic agents. In order to further define the importance of intracellular AUC of ITCs in stimulating cellular detoxification functions, we have compared the intracellular AUCs and the inducer activities of four common dietary ITCs, allyl-ITC, benzyl-ITC, phenethyl-ITC and sulforaphane [1-isothiocyanato-(4R,S)-(methylsulfinyl)butane], in mouse skin papilloma (PE) cells. When PE cells were incubated with 5 microM of each ITC for 24 h, significant elevations of glutathione content (1.8-4.3-fold), quinone reductase activity (2.1-5.4-fold) and glutathione transferase activity (0.8-1.5-fold) were observed. These elevations were closely correlated with the AUCs of the ITCs. Increasing intracellular AUC of a weaker ITC by multiple dosing also increased its inducer activity. Further studies revealed that the AUC-dependent elevation of the above elements were mediated by the DNA regulatory element EpRE/ARE. In human HepG2 cells, which were stably transfected with a reporter construct under EpRE/ARE control, the intracellular AUC of the four ITCs closely correlated with the levels of reporter gene product (green fluorescent protein). These results showed that cellular accumulation levels of ITCs determine their activity in inducing cellular detoxification capacity and suggested that the intracellular AUC might be a valuable biomarker of the Phase 2 enzyme inducer activity of ITCs.
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PMID:Total intracellular accumulation levels of dietary isothiocyanates determine their activity in elevation of cellular glutathione and induction of Phase 2 detoxification enzymes. 1175 29

Based on the potential cancer chemopreventive activity of resveratrol, a trihydroxystilbene with the induction of quinone reductase activity, this study was designed to determine if stilbene-related compounds were inducers of phase II detoxifying metabolic enzyme quinone reductase (QR) in the mouse hepatoma Hepa 1c1c7 cells. Among the thirteen compounds tested, several compounds including 3,4,5,3',5'-pentamethoxy-trans-stilbene were found to potentially induce QR activity in this cell line. In addition, substitution with 3-thiofurane ring instead of phenyl ring in the stilbene skeleton also exhibited potential induction of QR activity. This result will give primary information to design the potential inducers of QR activity in the stilbene analogs.
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PMID:Induction of quinone reductase activity by stilbene analogs in mouse Hepa 1c1c7 cells. 1179 42

Pure thiosulfinates, R-S(O)S-R (2), where R = Me (2a), Pr (2b), or All (2c), at levels up to 4 mM were not capable of scavenging hydrogen peroxide or superoxide anion. Relative to standard antioxidants (ascorbic acid, n-propyl gallate, butylated hydroxytoluene, Trolox, and reduced glutathione), these thiosulfinates were 1-3 orders of magnitude less efficient at reducing 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 0.5-2 orders of magnitude less efficient at quenching singlet oxygen, and about equally effective at scavenging hydroxyl radical. Generally, AllS(O)SAll (2c) was the most effective and PrS(O)SPr (2b) was the least effective thiosulfinate in these assays, except that MeS(O)SMe (2a) exhibited no quenching effect toward singlet oxygen. These thiosulfinates were also incapable at levels up to 0.1 mM (where they were toxic) of in vitro induction of quinone reductase (QR) in murine hepatoma (hepa 1c1c7) cells. However, S-1-propenyl-L-cysteine sulfoxide (isoalliin, 1a) and cycloalliin (3) induced QR in this system at 2 mM and 1 mM, respectively, although doubling of QR required levels of 10-15 mM.
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PMID:Antioxidant functions of selected allium thiosulfinates and S-alk(en)yl-L-cysteine sulfoxides. 1195 10

Thirty-seven naturally occurring withanolides (1-37), previously isolated in our laboratories, were evaluated for their potential to induce quinone reductase with cultured murine hepatoma cells (Hepa 1c1c7). Spiranoid (29, 32) and 18-functionalized withanolides (2-5, 7-9, 24) were found to be potent inducers of the enzyme, while 5alpha-substituted derivatives exhibited weak activity. Preliminary studies were performed with compound 29 to evaluate enzyme-inducing capacity in multiple organ sites of BALB/c mice. Significant induction was observed in liver and colon, but not in lung, stomach, or mammary gland.
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PMID:Induction of quinone reductase by withanolides. 1202 40

To determine whether radiographic images after radiofrequency (RF)-induced coagulation necrosis are correlated with the pathologic effects, we evaluated the morphology and histologic characteristics of RF ablation lesions over a 6-month follow-up period and compared the results with those of radiologic studies. Thirty-three hepatocellular carcinoma (HCC) tumors with a maximum diameter of 3 cm or less were treated percutaneously by using RF ablation in 26 patients. Six treated tumors were resected 4 weeks after ablation; the remaining 27 treated tumors underwent a biopsy procedure by using an 18-gauge fine needle 3 days, 4 weeks, and 24 weeks after ablation. The excised or biopsied lesions were examined by using histologic methods; the findings were then compared with those of contrast-enhanced computed tomography (CT). Three days after ablation, a core of hypoattenuation surrounded by an enhanced/hemorrhagic rim was observed on the contrast-enhanced CT images. Hematoxylin-eosin-stained specimens were inconclusive as to whether or not cellular viability remained; however, cell viability as determined by the presence of histochemical (lactate-dehydrogenase, maleate-dehydrogenase, and the reduced form of nicotinamide-adenine dinucleotide phosphate [NADPH]-diaphorase) stains was absent, suggesting 100% cellular destruction in the ablated lesion. Four and 24 weeks after ablation, the sizes of the ablated lesions were progressively smaller on the CT images; the histochemical stains remained superior to the hematoxylin-eosin stains for obtaining a definite diagnosis of cell death. We conclude that irreversible cellular destruction, as determined by the absence of positive histochemical staining patterns, was useful for evaluating the pathologic thermal effect of RF ablation. These pathologic findings can be correlated with those of contrast-enhanced CT.
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PMID:Treatment of hepatocellular carcinoma with radiofrequency ablation: radiologic-histologic correlation during follow-up periods. 1202 32

Natural isothiocyanates, produced during plant tissue damage from methionine-derived glucosinolates, are potent inducers of mammalian phase 2 detoxification enzymes such as quinone reductase (QR). A greatly simplified bioassay for glucosinolates based on induction and colorimetric detection of QR activity in murine hepatoma cells is described. It is demonstrated that excised leaf disks of Arabidopsis thaliana (ecotype Columbia) can directly and reproducibly substitute for cell-free leaf extracts as inducers of murine QR, which reduces samples preparation to a minimum and maximizes throughput. A comparison of 1 and 3 mm diameter leaf disks indicated that QR inducer potency was proportional to disk circumference (extent of tissue damage) rather than to area. When compared to the QR inducer potency of the corresponding amount of extract, 1 mm leaf disks were equally effective, whereas 3 mm disks were 70% as potent. The QR inducer potency of leaf disks correlated positively with the content of methionine-derived glucosinolates, as shown by the analysis of wild-type plants and mutant lines with lower or higher glucosinolate content. Thus, the microtitre plate-based assay of single leaf disks provides a robust and inexpensive visual method for rapidly screening large numbers of plants in mapping populations or mutant collections and may be applicable to other glucosinolate-producing species.
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PMID:Direct analysis of single leaf disks for chemopreventive glucosinolates. 1209 5

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD), a ubiquitous environmental pollutant, elicits a variety of toxicities and is a well-known carcinogen. TCDD alters the expression of many genes including CYP1A1/2, CYP1B1, glutathione S-transferase Ya, aldehyde-3-dehydrogenase, NAD(P)H:quinone oxidoreductase, transforming growth factor (TGF)-alpha and TGF-beta. The present study was aimed at characterization of TCDD to induce plasminogen activator inhibitor-1 (PAI-1) in mouse hepatoma cell lines. A Hepa1c1c7 wild-type cell [H1(wt)], an aryl hydrocarbon receptor (AhR)-deficient mutant [H1(AhR(-))] and an AhR nuclear translocator (Arnt)-deficient mutant [H1(Arnt(-))] were used for this study. TCDD induced PAI-1 in H1(wt) cells, but not in H1(AhR(-)) and H1(Arnt(-)) mutants, indicating a functional role of the AhR-Arnt complex in this effect. Cycloheximide (CHX) treatment resulted in increased PAI-1 mRNA induction, indicating that this response to TCDD is a direct effect on transcription and not a secondary effect mediated by other TCDD-induced proteins. Transfection with PAI-1 promoter led to increased PAI-1 promoter activity in H1(wt) cells treated with TCDD, but no such effect occurred in H1(AhR(-)) or H1(Arnt(-)) cells, implying involvement of the AhR and Arnt. In addition, alpha-naphthoflavone and phenanthroline, two AhR antagonists, each blocked the enhancing effect of TCDD on PAI-1 promoter-coupled luciferase activity in H1(wt) cells. PAI-1 promoter deletion analysis indicated that TCDD-induced PAI-1 transcription was distinctly different from TGF-beta-dependent PAI-1 transcription, particularly in the region between -161 to +73. In summary, TCDD induced the PAI-1 gene directly via an AhR- and Arnt-dependent mechanism, which was distinctly different from TGF-beta-driven PAI-1 transcription.
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PMID:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces plasminogen activator inhibitor-1 through an aryl hydrocarbon receptor-mediated pathway in mouse hepatoma cell lines. 1211 Oct 5

Two new compounds, an ent-isopimarane-type diterpene, 3alpha,12alpha-dihydroxy-ent-8(14),15-isopimaradien-18-al (1), and a dihydrobenzo[b]furan neolignan, (-)-trans-9-acetyl-4,9'-di-O-methyl-3'-de-O-methyldehydrodiconiferyl alcohol (2), along with five known compounds, 7,7'-dihydroxy-6,8'-bicoumarin (bicoumol) (3), 3,4-dimethoxycinnamaldehyde (4), 6-hydroxy-7-methoxycoumarin (isoscopoletin), N-butylaniline, and vanillin, have been isolated from an ethyl acetate-soluble extract of the stem wood of Euphorbiaquinquecostata. The structures of compounds 1 and 2 were elucidated on the basis of spectroscopic data interpretation, and single-crystal X-ray diffraction analysis was used to confirm the structure and relative stereochemistry of 1. The absolute configuration of 1 was established by a convenient Mosher ester procedure in which the sample was treated with MTPA chlorides in deuterated pyridine directly in NMR tubes. All isolates were evaluated for the induction of quinone reductase in Hepa1c1c7 hepatoma cells and for the inhibition of the transformation of murine epidermal JB6 cells.
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PMID:New chemical constituents of Euphorbia quinquecostata and absolute configuration assignment by a convenient Mosher ester procedure carried out in NMR tubes. 1235 Jan 47

A new bicyclic diarylheptanoid, rel-(3S,4aR,10bR)-8-hydroxy-3-(4-hydroxyphenyl)-9-methoxy-4a,5,6,10b-tetrahydro-3H-naphtho[2,1-b]pyran (1), as well as four known compounds, 1,2-dihydro-1,2,3-trihydroxy-9-(4-methoxyphenyl)phenalene (2), hydroxyanigorufone (3), 2-(4-hydroxyphenyl)naphthalic anhydride (4), and 1,7-bis(4-hydroxyphenyl)hepta-4(E),6(E)-dien-3-one (5), were isolated from an ethyl acetate-soluble fraction of the methanol extract of the fruits of Musa x paradisiaca cultivar, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structure and relative stereochemistry of compound 1 were elucidated unambiguously by one- and two-dimensional NMR experiments ((1)H NMR, (13)C NMR, DEPT, COSY, HMQC, HMBC, and NOESY) and single-crystal X-ray diffraction analysis. Isolates 1-5 were evaluated for their potential cancer chemopreventive properties utilizing an in vitro assay to determine quinone reductase induction and a mouse mammary organ culture assay.
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PMID:Constituents of Musa x paradisiaca cultivar with the potential to induce the phase II enzyme, quinone reductase. 1238 Nov 12


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