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)

Free-radical scavenging, reducing, and phase II enzyme-inducing activities of aqueous and 5% aqueous ethanol extracts of freeze-dried root tissue of four beet (Beta vulgaris L.) strains (red, white, orange, and high-pigment (red) phenotypes) were determined. Aqueous and ethanolic tissue extracts of the regular and high-pigment red phenotypes were most capable of inhibiting metmyoglobin/H(2)O(2)-mediated oxidation of 2-2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH)-mediated bleaching of beta-carotene. These same extracts were also most efficient at reducing ABTS radical cation and inducing quinone reductase in murine hepatoma (Hepa 1c1c7) cells in vitro.
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PMID:Phase II enzyme-inducing and antioxidant activities of beetroot (Beta vulgaris L.) extracts from phenotypes of different pigmentation. 1240 65

The anticarcinogenic properties of broccoli are believed to be due to modification of detoxification enzymes by a group of isothiocyanates, hydrolysis products of glucosinolates, particularly sulforaphane. We previously showed that the nitrile crambene (1-cyano-2-hydroxy-3-butene), present in most Brassica vegetables, induces hepatic quinone reductase activity when administered to rats. In this study, we compared the effects of seven daily oral doses of crambene (50 mg/kg rat/day) and sulforaphane (50 mg/kg rat/day) on induction of hepatic quinone reductase activity in Fischer 344 rats. The two treatments produced similar effects, with crambene and sulforaphane producing 1.5- and 1.7-fold induction in hepatic quinone reductase activity, respectively. Additionally, we evaluated the effect of crambene on quinone reductase activity in Hepa 1c1c7 cells, because this system had been shown to possess high sensitivity to sulforaphane and is commonly used for screening anticarcinogenic compounds. Crambene (5 mM) induced quinone reductase activity and caused cell cycle arrest in the G2/M phase in mouse Hepa 1c1c7 cells, rat H4IIEC3 cells, and human Hep G2 cells (> 95% viability). Doses of crambene needed for induction of quinone reductase in cell culture were approximately 100-fold greater than effective doses of sulforaphane. These findings indicate that hepatoma cell lines may not accurately reflect relative potency of anticarcinogens in Fischer 344 rats.
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PMID:The cruciferous nitrile crambene has bioactivity similar to sulforaphane when administered to Fischer 344 rats but is far less potent in cell culture. 1241 65

Three new prenylated dihydrochalcones, (+/-)-nicolaioidesins A, B, and C (1-3), as well as a new natural product, 5-styrylfuran-2-carboxylic acid methyl ester (4), along with four known compounds, 2'-hydroxy-4',6'-dimethoxychalcone (5), (+/-)-5-hydroxy-7-methoxyflavanone (6), (+/-)-5-hydroxy-7,4'-dimethoxyflavanone, and panduratin A, were isolated from the roots of Renealmia nicolaioides, using a bioassay to determine the induction of quinone reductase (QR) activity with cultured Hepa lclc7 mouse hepatoma cells. Among these isolates, 5 and 6 induced QR activity, with observed concentrations to double activity (CD) values of 1.7 and 0.9 microg/mL, respectively, while the other constituents were not regarded as being active (CD >10 microg/mL). The chemical structures of 1-4 were elucidated by spectroscopic methods. A biogenetic pathway for the formation of (+/-)-nicolaioidins A-C (1-3) is proposed.
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PMID:Activity-guided isolation of constituents of Renealmia nicolaioides with the potential to induce the phase II enzyme quinone reductase. 1244 86

Over 60 different samples comprising 35 distinct honeys were evaluated for their ability to induce mammalian phase 2 detoxication enzymes using a microtiter plate assay of quinone reductase (QR) induction with murine hepatoma cells in microtiter plates. This assay has been used extensively to identify and isolate a variety of natural and synthetic inducers from plants. All 35 honeys examined induced elevations of mammalian QR activity ranging from 153 to 2155 units/g with a mean of 630 and a median of 417 units/g. The concentrations for doubling the QR activity (CD) of certain of the prominent flavonoids found in honey were also assessed (pinostrobin, 0.5 microM; pinocembrin, 110 microM; chrysin, 25 microM) and compared to those of related, more commonly described flavonoids such as quercetin (2.7 microM) and myricetin (58 microM). On the basis of the extremely high QR inducing potency of one of these compounds, pinostrobin (5-hydroxy-7-methoxyflavanone), a bioassay-guided search was conducted which revealed a dietary source of pinostrobin, Boesenbergia pandurata (fingerroot), with extraordinarily high ability to induce mammalian phase 2 detoxication enzymes. Although the QR inducing activity of buckwheat honeys was 2155 +/- 951 units/g (n = 8 samples), which is less than 10% of the average values obtained from fresh broccoli, the potency of fingerroot rhizomes (ca. 110,000 units/g) is even higher than that of broccoli and the potencies of fingerroot oil and powdered rhizome (ca. 500,000 units/g) rival that of broccoli sprouts.
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PMID:Pinostrobin from honey and Thai ginger (Boesenbergia pandurata): a potent flavonoid inducer of mammalian phase 2 chemoprotective and antioxidant enzymes. 1245 78

Cell-based models have been used extensively in screening novel bioactive chemical entities. In this study, seven well-established mammalian cell lines, which have different origins, were utilized to compare their responses to the treatments of three detoxifying enzyme inducers, tert-butylhydroquinone (tBHQ), beta-naphthoflavone (beta-NF), and sulforaphane (SUL), which are potential chemopreventive compounds. The enzymatic activities of glutathione s-transferase (GST), NAD(P)H:quinone oxidoreductase (QR), aldehyde reductase (AR), and glutathione reductase (GR) were measured by kinetics methods using UV-Vis spectroscopy, and analyzed statistically by Student's t-test. Among these mammalian cell lines, the mouse hepatoma Hepa1c1c7 cells were the most robust and sensitive cells, which had higher basal as well as upregulated enzymatic activities. In human cell lines, the prostate LNCaP and hepatic HepG2 cells were also very responsive to the inducers. The results suggested that different cell lines responded differently to individual detoxifying gene inducer, and the selection of appropriate cell line is important for screening potential chemopreventive agents.
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PMID:Differential responses from seven mammalian cell lines to the treatments of detoxifying enzyme inducers. 1262 44

Identification and use of effective cancer chemopreventive agents have become an important issue in public health-related research. For identification of potential cancer chemopreventive constituents we have set up a battery of cell- and enzyme-based in vitro marker systems relevant for prevention of carcinogenesis in vivo. These systems include modulation of drug metabolism (inhibition of Cyp1A activity, induction of NAD(P)H:quinone reductase (QR) activity in Hepa1c1c7 murine hepatoma cell culture), determination of radical scavenging (DPPH scavenging) and antioxidant effects (scavenging of superoxide anion-, hydroxyl- and peroxyl-radicals), anti-inflammatory mechanisms (inhibition of lipopolysaccharide (LPS)-mediated nitric oxide (NO) generation by inducible NO synthase (iNOS) in Raw 264.7 murine macrophages, cyclooxygenase-1 (Cox-1) inhibition), and anti-tumor promoting activities (inhibition of phorbol ester-induced ornithine decarboxylase (ODC) activity in 308 murine keratinocytes). We have tested a series of known chemopreventive substances belonging to several structural classes as reference compounds for the identification of novel chemopreventive agents or mechanisms. These include organosulfur compounds (phenethylisothiocyanate (PEITC), diallylsulfide, diallyldisulfide), terpenes (limonene, perillyl alcohol, oleanolic acid, 18-beta-glycyrrhetinic acid), short-chain fatty acids (sodium butyrate), indoles (indole-3-carbinol), isoflavonoids (quercetin, silymarin, genistein), catechins ((-)-epigallocatechin gallate (EGCG)), simple phenols (ellagic acid, resveratrol, piceatannol, curcumin), pharmaceutical agents (piroxicam, acetylsalicylic acid, tamoxifen), and vitamins/derivatives (ascorbic acid, Trolox). We confirmed known chemopreventive mechanisms of these compounds. Additionally, we could demonstrate the usefulness of our approach by identification of hitherto unknown mechanisms of selected agents. As an example, we detected anti-inflammatory properties of PEITC, based on NF-kappaB-mediated inhibition of NO production. Further, PEITC inhibited phorbol ester-induced superoxide anion radical production in granulocytes, and ODC induction in the 308 cell line. These mechanisms might contribute to the chemopreventive potential of PEITC.
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PMID:Mechanism-based in vitro screening of potential cancer chemopreventive agents. 1262 14

Activity-monitored fractionation of a CHCl(3)-soluble extract of Deprea subtriflora using a quinone reductase induction assay led to the purification of subtrifloralactones A-J (1-10), 10 novel C-18 norwithanolides based on a new C(27) skeleton. These compounds were characterized by spectroscopic and chemical studies, and single-crystal X-ray diffraction analysis was used to confirm the structures of 1 and 4. Compounds 1-10 were evaluated for their cancer chemopreventive activity in terms of their ability to induce quinone reductase activity with cultured murine hepatoma cells, and compounds 1 and 6 were found to be highly effective.
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PMID:Activity-guided isolation of novel norwithanolides from depreasubtriflora with potential cancer chemopreventive activity. 1263 2

Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a natural phytoalexin found in grapes and wine. It has antioxidant and antiproliferative activities, and has been shown to induce NAD(P)H:quinone oxidoreductase, also known as DT-diaphorase, in cultured mouse hepatoma cells. DT-diaphorase is a detoxifying enzyme for quinone-containing substances, due to its ability to prevent their one-electron reduction and the consequent generation of reactive oxygen species (ROS). The aim of the present study was to investigate whether oral administration of trans-resveratrol to guinea pigs (60 mg/l in tap water for 16 days, ad libitum) increases cardiac DT-diaphorase and, consequently, reduces the response of isolated atria to 2-methyl-1,4-naphthoquinone (menadione), the positive inotropic effect of which is related to the amount of ROS generated by its cardiac metabolism. In the cardiac tissue of resveratrol-treated animals, DT-diaphorase activity was significantly higher than that measured in control animals, the V(max) of the enzyme reaction being 75.47 +/- 3.87 and 50.73 +/- 0.63 nmoles/mg protein/min, respectively (p < 0.05). Resveratrol administration also significantly increased the activity of cardiac catalase (32.20 +/- 2.39 vs. 25.14 +/- 3.85 units/mg protein in treated and control animals, respectively; p < 0.001). As a consequence, menadione metabolism by the cardiac homogenate obtained from resveratrol-treated animals generated a smaller amount of ROS and, in electrically driven left atria, menadione produced a significantly lower increase in the force of contraction than in atria isolated from control animals. These results indicate that oral administration of resveratrol exerts cardioprotection against ROS-mediated menadione toxicity.
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PMID:Oral administration of trans-resveratrol to guinea pigs increases cardiac DT-diaphorase and catalase activities, and protects isolated atria from menadione toxicity. 1267 91

Activity-guided fractionation of an EtOAc-soluble extract of the leaves of Muntingia calabura collected in Peru, using an in vitro quinone reductase induction assay with cultured Hepa 1c1c7 (mouse hepatoma) cells, resulted in the isolation of a flavanone with an unsubstituted B-ring, (2R,3R)-7-methoxy-3,5,8-trihydroxyflavanone (5), as well as 24 known compounds, which were mainly flavanones and flavones. The structure including absolute stereochemistry of compound 5 was determined by spectroscopic (HRMS, 1D and 2D NMR, and CD spectra) methods. Of the isolates obtained, in addition to 5, (2S)-5-hydroxy-7-methoxyflavanone, 2',4'-dihydroxychalcone, 4,2',4'-trihydroxychalcone, 7-hydroxyisoflavone and 7,3',4'-trimethoxyisoflavone were found to induce quinone reductase activity.
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PMID:Activity-guided isolation of the chemical constituents of Muntingia calabura using a quinone reductase induction assay. 1273 82

Sulforaphane (SF), a glucosinolate-derived isothiocyanate found in cruciferous vegetables, is considered an anticarcinogenic component in broccoli. Sulforaphane induces a battery of detoxification enzymes, including quinone reductase (QR). Induction is thought to be mediated through a common regulatory region termed the antioxidant response element (ARE). To test the hypothesis that the antioxidant selenoprotein thioredoxin reductase (TR) may be induced as part of this coordinated host-defense response to dietary anticarcinogenic compounds, TR activity was measured in livers of rats pair-fed diets containing SF and/or broccoli (n = 6/group). At the doses used, neither SF nor broccoli alone significantly elevated TR activity, whereas treatments containing both broccoli and SF caused a significant increase in TR activity. Glutathione peroxidase (GSH-Px), a second selenium-dependant enzyme with antioxidant activity, was downregulated in rats fed both SF and broccoli, compared to the control diet.A second experiment, using mouse hepatoma Hepa1c1c7 cells, tested whether an interaction exists between selenium (Se) and SF in TR inducibility, since Se is known to induce TR activity. Selenium (2.5 &mgr;M) plus SF (2.0 &mgr;M) caused significantly greater TR activity than either treatment alone. All treatments with added Se or SF caused significantly greater TR activities than no Se or SF treatment. Glutathione peroxidase activity was elevated by Se, but not by SF. These data suggest that TR, known to be regulated by Se, is also upregulated as part of a host response to the dietary anticarcinogen SF, a trait not shared by another Se-dependent enzyme, GSH-Px.
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PMID:Induction of hepatic thioredoxin reductase activity by sulforaphane, both in Hepa1c1c7 cells and in male Fisher 344 rats. 1274 46


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