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)

Activity-guided fractionation of the EtOAc-soluble extract of the whole plants of Sida acuta using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells, led to the isolation of ten active compounds of previously known structure, quindolinone (1), cryptolepinone (2), 11-methoxyquindoline (3), N-trans-feruloyltyramine (4), vomifoliol (5), loliolide (6), 4-ketopinoresinol (7), scopoletin (8), evofolin-A (9), and evofolin-B (10), along with five inactive compounds of known structure, ferulic acid, sinapic acid, syringic acid, (+/-)-syringaresinol, and vanillic acid. These isolates were identified by physical and spectral data measurement. A new derivative of quindolinone, 5,10-dimethylquindolin-11-one (1a) was synthesized and characterized spectroscopically. Of the active substances, compounds 1-3 and 1a exhibited the most potent QR activity, with observed CD (concentration required to double induction) values ranging from 0.01 to 0.12 microg/mL. Six compounds were then evaluated in a mouse mammary organ culture assay, with cryptolepinone (2), N-trans-feruloyltyramine (4), and 5,10-dimethylquindolin-11-one (1a) found to exhibit 83.3, 75.0, and 66.7% inhibition of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions, respectively, at a dose of 10 microg/mL.
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PMID:Compounds obtained from sida acuta with the potential to induce quinone reductase and to inhibit 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in a mouse mammary organ culture model. 1296 90

A new butenylflavanone, (2S)-5-hydroxy-7-methoxy-8-[(E)-3-oxo-1-butenyl]flavanone (1), and a new rotenoid, 4',5'-dihydro-11,5'-dihydroxy-4'-methoxytephrosin (2), as well as three active flavonoids of previously known structure, isoliquiritigenin (3), genistein (4), and chrysoeriol (5), along with nine known inactive compounds, alpha-toxicarol (6), sumatrol, 6a,12a-dehydro-alpha-toxicarol, 11-hydroxytephrosin, obovatin, marmesin, lupenone, benzyl benzoate, and benzyl trans-cinnamate, were isolated from an ethyl acetate-soluble extract of the stems of Tephrosia toxicaria, 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. All isolates were evaluated for their potential cancer chemopreventive properties utilizing an in vitro assay to determine quinone reductase induction. Selected compounds were tested in a mouse mammary organ culture assay to evaluate the inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced preneoplastic lesions.
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PMID:Potential cncer chemopreventive flavonoids from the stems of Tephrosia toxicaria. 1451 May 90

Activity-guided fractionation of the petroleum ether and ethyl acetate extracts of the stem bark of Pongamia pinnata, using cultured Hepa 1c1c7 mouse hepatoma cells to evaluate quinone reductase (QR) inducing activity, led to the isolation of four new flavanone derivatives (1-4), one new flavone (5), one new chalcone (6), and 13 known compounds of the flavonoid, terpenoid, and fatty acid types. The structures of 1-6 were characterized on the basis of the interpretation of their spectroscopic data. The absolute stereochemistry of compounds 1-4 was determined from their CD data and by Mosher ester determination. All isolates obtained were evaluated in the quinone reductase induction assay.
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PMID:Constituents of the stem bark of Pongamia pinnata with the potential to induce quinone reductase. 1451 May 96

Activity-guided fractionation of the leaves of Macaranga triloba, using an in vitro bioassay based on the inhibition of cyclooxygenase-2, resulted in the isolation of a rotenoid, 4,5-dihydro-5'alpha-hydroxy-4'alpha-methoxy-6a,12a-dehydro-alpha-toxicarol (1), as well as 12 known compounds, (+)-clovan-2beta,9alpha-diol, ferulic acid, 3,7,3',4'-tetramethylquercetin, 3,7,3'-trimethylquercetin, 3,7-dimethylquercetin, abscisic acid, 1beta,6alpha-dihydroxy-4(15)-eudesmene, 3beta-hydroxy-24-ethylcholest-5-en-7-one, loliolide, scopoletin, taraxerol, and 3-epi-taraxerol. The structure of compound 1 was determined using spectroscopic methods. All isolates were evaluated for their potential to inhibit cyclooxygenases-1 and -2 by measuring PGE(2) production, and to induce quinone reductase in cultured Hepa 1c1c7 mouse hepatoma cells.
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PMID:Potential cancer chemopreventive constituents of the leaves of Macaranga triloba. 1475 6

Activity-guided fractionation of the EtOAc-soluble extract of the stems of Couepia ulei, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells led to the isolation of two active compounds, a new natural product, erythro-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-1-ol (1), and a known compound, evofolin-B (2), along with five inactive compounds all of known structure, viz., betulinic acid, oleanolic acid, pomolic acid, (+/-)-syringaresinol, and ursolic acid. These isolates were identified by analysis of physical and spectral data. Compounds 1 and 2 exhibited QR inducing activity, with observed CD (concentration required to double induction) values of 16.7 and 16.4 microM, respectively.
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PMID:Phenolic compounds obtained from stems of Couepia ulei with the potential to induce quinone reductase. 1502 17

Sulforaphane, an isothiocyanate from broccoli, is one of the most potent food-derived anticarcinogens. This compound is not present in the intact vegetable, rather it is formed from its glucosinolate precursor, glucoraphanin, by the action of myrosinase, a thioglucosidase enzyme, when broccoli tissue is crushed or chewed. However, a number of studies have demonstrated that sulforaphane yield from glucoraphanin is low, and that a non-bioactive nitrile analog, sulforaphane nitrile, is the primary hydrolysis product when plant tissue is crushed at room temperature. Recent evidence suggests that in Arabidopsis, nitrile formation from glucosinolates is controlled by a heat-sensitive protein, epithiospecifier protein (ESP), a non-catalytic cofactor of myrosinase. Our objectives were to examine the effects of heating broccoli florets and sprouts on sulforaphane and sulforaphane nitrile formation, to determine if broccoli contains ESP activity, then to correlate heat-dependent changes in ESP activity, sulforaphane content and bioactivity, as measured by induction of the phase II detoxification enzyme quinone reductase (QR) in cell culture. Heating fresh broccoli florets or broccoli sprouts to 60 degrees C prior to homogenization simultaneously increased sulforaphane formation and decreased sulforaphane nitrile formation. A significant loss of ESP activity paralleled the decrease in sulforaphane nitrile formation. Heating to 70 degrees C and above decreased the formation of both products in broccoli florets, but not in broccoli sprouts. The induction of QR in cultured mouse hepatoma Hepa lclc7 cells paralleled increases in sulforaphane formation.
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PMID:Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli. 1518 12

Epidemiological studies show that cruciferous vegetables play a role in dietary protection against cancers. The protective effects of crucifers are thought to be associated with secondary metabolites termed glucosinolates, the hydrolysis products of which upregulate hepatic detoxification enzymes. Crambene, a nitrile product of the glucosinolate progoitrin, increases hepatic quinone reductase (QR) when included in the diet of animals. Here we evaluate the mechanism of upregulation of detoxification enzymes by crambene. The regulatory region of the QR gene contains two response elements, the antioxidant response element (ARE) and the xenobiotic response element (XRE), that respond to glucosinolate hydrolysis products. We compared upregulation of QR mRNA expression by crambene in wild-type and Ah receptor-deficient mouse hepatoma cell lines. Both cell lines showed a similar increase in QR mRNA, suggesting that the Ah receptor-dependent XRE pathway is not required for crambene to act. Transient transfection of HepG2 cells with reporter constructs containing portions of the 5' regulatory region of the rat QR gene confirmed this, revealing that crambene significantly activated ARE, but not XRE, in a dose-dependent manner. Furthermore, both indole-3-carbinol (I3C) and I3C acid condensates (I3C-A) activated the ARE for QR gene expression whereas only I3C-A activated the XRE at the concentrations studied. In addition, co-treatment with crambene and I3C-A caused synergistic increases in QR transcriptional activity and mRNA levels in HepG2 cells. Based on these findings, we propose that synergistic upregulation of QR is due to co-activation of the ARE and the XRE by crambene and I3C-A.
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PMID:Crambene, a bioactive nitrile derived from glucosinolate hydrolysis, acts via the antioxidant response element to upregulate quinone reductase alone or synergistically with indole-3-carbinol. 1520 47

It has been previously demonstrated in a human-derived hepatoma cell line (HepG2) that juices from cruciferous vegetables protect against the genotoxicity caused by dietary carcinogens. HepG2 cells possess different enzymes involved in the biotransformation of xenobiotics. Therefore, we investigated the effect of cruciferous juices on the activities of CYP 1A and several phase II enzymes in this cell model. For each experiment, 1 x 10(6) cells were seeded on Petri dishes. After 2 days, the juices (0.5-8 microl/ml of culture medium) were added for 48 h prior to cell harvesting. The addition of juice from water cress (Nasturtium officinalis R. Br) significantly increased the activities of ethoxyresorufin-O-deethylase at high doses only and NAD(P)H-quinone reductase in a dose-dependent manner (1.8- and 5-fold, respectively). The addition of juice from garden cress (Lepidum sativum L.) significantly increased the activities of NAD(P)H-quinone reductase and UDP-glucuronosyl-transferase with a maximal effect around the dose of 2 microl/ml juice (1.4- and 1.2-fold, respectively) while the other enzymes were not altered. Mustard (Sinapis alba L.) juice increased the activities of NAD(P)H-quinone reductase (2.6-fold at the dose of 8 microl/ml), and N-acetyl-transferase (1.4-fold at the dose of 8 microl/ml) in a dose-dependent manner while a maximal induction of UDP-glucuronosyl-transferase was obtained with a dose of 2 microl/ml (1.8-fold). These observations show that the three juices have different induction profiles: only water cress acted as a bifunctional inducer by enhancing both phase I and phase II enzymes. As a consequence, each juice may preferentially inhibit the genotoxicity of specific compounds.
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PMID:The activities of several detoxication enzymes are differentially induced by juices of garden cress, water cress and mustard in human HepG2 cells. 1556 Aug 88

Broccoli belongs to a group of vegetables termed cruciferous vegetables and characterized by their glucosinolate content. These glucosinolates are secondary metabolites that, upon hydrolysis, release bioactive isothiocyanates (ITCs). Bioactive ITCs are considered to protect the body from cancer by inducing detoxification enzymes such as quinone reductase (QR). This has the potential to make dietary choice a powerful strategy for achieving protection against carcinogenesis, mutagenesis, and other forms of toxicity from xenobiotic electrophiles and reactive forms of oxygen. The bioactive ITC sulforaphane (SF) is the hydrolysis product of glucoraphanin, the predominant aliphatic glucosinolate in broccoli. Because SF appears more potent than many other ITCs in induction of detoxification enzymes, it may have potential as a dietary cancer-preventative agent. One potential concern is that SF is highly reactive and has a very short half-life in the body, forming a glutathione conjugate that is further metabolized to the N-acetyl-L-cysteine conjugate (SF-NAC), the major excretory product found in the urine. However, the conjugate is a reversible complex, able to release free SF. The objective of this study was to compare QR-inducing activity by SF and its major metabolite SF-NAC, in murine hepatoma cells. Both SF and SF-NAC caused dose-related cell growth inhibition and QR induction. SF, 1 and 2 microM, resulted in a 3.0- and 3.5-fold induction of QR, respectively, and the same concentrations of SF-NAC caused a similar, although somewhat greater, induction of QR, 3.8- and 4.5-fold, respectively. These results strengthen the basis for considering that an effective therapeutic form of SF may be the ITC conjugate, formed in situ or given in place of purified ITC as prophylactic treatment to individuals at high risk for cancer.
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PMID:Induction of quinone reductase by sulforaphane and sulforaphane N-acetylcysteine conjugate in murine hepatoma cells. 1611 12

Chemoprevention can be defined as an intervention in the carcinogenic process by use of natural or synthetic substances. Induction of Phase II enzyme is an important mechanism of chemoprevention. In the present studies we have synthesized several derivatives of (+)(-) 4-methylsulfinyl-1-(S-methyldithiocarbamyl)-butane (sulforamate) and evaluated their effectiveness as monofunctional inducer of the NAD(P)H Quinone oxidoreductase [quinone reductase (QR)] a phase II enzyme in cultured Hepa1c1c7 murine hepatoma cells. The cytotoxicity of some of the derivatives was strongly reduced in comparison to [(-)-1-isothiocyanato-4(R)-(methylsulfinyl)butane] (sulforaphane). However, the induction potential of these compounds was comparable to sulforaphane. On the basis of these results sulforamate derivatives can be regarded as simple, inexpensive and readily available chemopreventive agents.
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PMID:Cancer chemopreventive activity of sulforamate derivatives. 1630 Aug 58


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