Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

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

A new cassane diterpene, dipteryxic acid (1), and a new isoflavonolignan, 5-methoxyxanthocercin A (2), as well as four known active compounds, isoliquiritigenin (3), 6,4'-dihydroxy-3'-methoxyaurone (4), sulfuretin (5), and (+/-)-balanophonin (6), and five known inactive compounds, butin, eriodictyol, 7-hydroxychromone, 7,3'-dihydroxy-8,4'-dimethoxyisoflavone, and (-)-lariciresinol, were isolated from an ethyl acetate-soluble extract of the seeds of Dipteryx odorata, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. Single-crystal X-ray diffraction analysis was used to confirm the relative stereochemistry of compound 1. Selected compounds (3-5) were evaluated in a mouse mammary organ culture assay, with isoliquiritigenin (3) found to exhibit 76% inhibition at a dose of 10 microg/mL.
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PMID:Potential cancer chemopreventive constituents of the seeds of Dipteryx odorata (tonka bean). 1276 87

The increased expression of quinone reductase (QR) has been associated with anticarcinogenic processes. The aim of this study was to explore the roles of the cruciferous vegetable-derived indoles, indole-3-carbinol (I3C) and indolo[3.2-b]carbazole (ICZ), on the regulation of QR in both murine (Hepa-1) and human (HepG2) hepatoma cells. The results indicate that ICZ enhanced QR activity in both Hepa-1 and HepG2 cells, whereas its parent compound. I3C, had no significant effect on the induction of QR. Moreover, the ICZ-induced QR activity showed a higher response and expressed a more-significant dose-response in Hepa-1 cells. QR mRNA expression as analyzed by RT-PCR demonstrated a pattern similar to that of the enzyme activity. in conclusion, I3C did not show an enhancement effect on OR activity, but its acidic derivative, ICZ, increased the expression of QR mRNA, which then caused the augmentation of QR activity in Hepa-1 and HepG2 cells.
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PMID:Differential effects of vegetable-derived indoles on the induction of quinone reductase in hepatoma cells. 1277 14

Oltipraz, a promising cancer chemopreventive agent, has been recognized as a monofunctional inducer selectively activating phase II carcinogen-detoxifying enzymes via the antioxidant responsive element (ARE). However, we report here that oltipraz also induces rat glutathione S-transferase A5 (GSTA5), a potent phase II detoxifying enzyme, by means of the xenobiotic responsive element (XRE). Although an ARE sequence exists in the 5' upstream of the rGSTA5 gene, this cis-acting regulatory element loses its responsiveness to oltipraz treatment because of extensive mutations in its distal-half site. Our data indicate that a XRE sequence, located downstream of the transcription initiation site of the gene, is another oltipraz-responsive element. Electrophoretic mobility shift assay showed that oltipraz steadily induces XRE-aryl hydrocarbon receptor (AhR) binding, which can be blocked specifically by excess XRE oligonucleotides or by AhR antibody. By cloning different XREs into the pGL3-promoter vector, we found that oltipraz can activate XRE enhancers from several phase II drug metabolism enzymes, including rGSTA5, rGSTA2, NAD(P)H:quinone reductase, and it also activates XRE from the phase I metabolism enzyme CYP1A1. Oltipraz's effect on XRE is AhR-dependent and is independent of the presence of active CYP1A1. Reverse transcriptase-polymerase chain reaction experiments revealed that oltipraz induces gene expression of both phase I and II drug-metabolizing enzymes in rat hepatoma cells. Thus, we conclude that, like ARE, the XRE pathway constitutes an important part of the molecular mechanism contributing to oltipraz-induced expression of the phase II metabolism enzymes. Oltipraz is a bifunctional inducer, modulating both phase I and II drug-metabolizing enzymes to enhance carcinogen detoxification.
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PMID:Oltipraz is a bifunctional inducer activating both phase I and phase II drug-metabolizing enzymes via the xenobiotic responsive element. 1286 39

Two new C-18 norwithanolides based on a C(27) skeleton, subtrifloralactones K (1) and L (2), a new C-18 oxygenated withanolide, 13 beta-hydroxymethylsubtrifloralactone E (3), and a new alpha-ionone derivative, (+)-7 alpha,8 alpha-epoxyblumenol B (4), along with five known compounds, philadelphicalactone A (5), (2S,3S,4R)-2-[(2R)-2'-hydroxytetracosanoylamino]-1,3,4-octadecanetriol (6), trans-N-feruloyltyramine, cis-N-feruloyltyramine, and (S)-coriolic acid, were isolated from additional active fractions of the chloroform-soluble extract of Deprea subtriflora, using a quinone reductase (QR) induction assay as a monitor. The structures of compounds 1-4 were characterized by spectroscopic data interpretation. The potential cancer chemopreventive activities of all isolates in terms of their ability to induce QR activity with cultured Hepa 1c1c7 mouse hepatoma cells were evaluated.
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PMID:Isolation and characterization of miscellaneous secondary metabolites of Deprea subtriflora. 1293 30

Coussaric acid (1), a triterpenoid based on an ursane skeleton, and an oleanane-type triterpene acid, 3-epi-spathodic acid (2), as well as four known compounds, barbinervic acid, scutellaric acid, stigmasterol and stigmasterol glucoside, have been isolated from an EtOAc-soluble extract of the stems of Coussarea brevicaulis. The structures of compounds 1 and 2 were elucidated on the basis of spectroscopic investigation, and single-crystal X-ray crystallography was used to confirm the structure of 1. The absolute stereochemistry of 1 was established by chemical transformations and by the Mosher ester procedure. The potential of the isolates and chemical transformation products to induce quinone reductase was evaluated in mouse Hepa lclc7 hepatoma cells.
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PMID:Isolation and absolute stereochemistry of coussaric acid, a new bioactive triterpenoid from the stems of Coussarea brevicaulis. 1294 28


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