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)

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

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

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

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


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