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)

It has been proposed that persistent oxidative stress accounts for the increased levels of DNA damage in cancer tissues. We have examined the profile of anti-oxidant enzymes in a transplanted hepatic tumor model by injecting N1S1 rat hepatoma cells into the liver of Sprague-Dawley rats. The transplanted N1S1 tumors displayed characteristics resembling human hepatocellular carcinoma. The immunoreactivities of catalase (CAT), manganese-superoxide dismutase (Mn SOD), copper/zinc-SOD (Cu/Zn SOD), and glutathione peroxidase (GPx) were found to decrease significantly. The enzyme activity in tumors decreased 26.2-, 4.2-, 4.5-, and 5.4-fold for CAT, Mn SOD, Cu/Zn SOD, and GPx, respectively, relative to those in normal liver tissue from the same animals. In contrast, the mRNA levels of CAT and GPx in tumors decreased only 5- and 2-fold, respectively, and the mRNA levels of Cu/Zn SOD and Mn SOD showed either no change or an increase as compared to those of normal liver tissue. The contents of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and thiobarbituric acid-reactive substances (TBARS) were comparable to those of normal controls. Furthermore, mitochondrial production of superoxide in tumors was 4 times lower than that in normal tissues. In conclusion, the data indicate that the reduced activities of anti-oxidant enzymes in the N1S1 tumor did not cause significant oxidative stress.
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PMID:Oxidative stress is insignificant in N1S1-transplanted hepatoma despite markedly declined activities of the antioxidant enzymes. 1052 4

Persistent infection by hepatitis B virus (HBV) and exposure to chemical carcinogens correlates with the prevalence of hepatocellular carcinoma in endemic areas. The precise nature of the interaction between these factors is not known. Glutathione S-transferases (GST) are responsible for the cellular metabolism and detoxification of a variety of cytotoxic and carcinogenic compounds by catalysis of their conjugation with glutathione. Diminished GST activity could enhance cellular sensitivity to chemical carcinogens. We have investigated GST isozyme expression in hepatocellular HepG2 cells and in an HBV-transfected subline. Total GST activity and selenium-independent glutathione peroxidase activity are significantly decreased in HBV transfected cells. On immunoblotting, HBV transfected cells demonstrate a significant decrease in the level of GST Alpha class. Cytotoxicity assays reveal that the HBV transfected cells are more sensitive to a wide range of compounds known to be detoxified by GST Alpha conjugation. Although no significant difference in protein half-life between the two cell lines was found, semi-quantitative reverse transcription-polymerase chain reaction shows a reduced amount of GST Alpha mRNA in the transfected cells. Because the HBV x protein (HBx) seems to play a role in HBV transfection, we also demonstrated that expression of the HBx gene into HepG2 cells decreased the amount of GST Alpha protein. Transient transfection experiments using both rat and human GST Alpha (rGSTA5 and hGSTA1) promoters in HepG2 cells show a decreased CAT activity upon HBx expression, supporting a transcriptional regulation of both genes by HBx. This effect is independent of HBx interaction with Sp1. Treatment with oltipraz, an inducer of GST Alpha, partially overcomes the effect of HBx on both promoters. Promoter deletion studies indicate that oltipraz works through responsive elements distinct from AP1 or NF-kappaB transcription factors. Thus, HBV infection alters phase II metabolizing enzymes via different mechanisms than those modulated by treatment with oltipraz.
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PMID:Modulation of glutathione S-transferase alpha by hepatitis B virus and the chemopreventive drug oltipraz. 1093 96

The translation of mammalian selenoprotein mRNAs requires the 3' untranslated region that contains a selenocysteine insertion sequence (SECIS) element necessary for decoding an in-frame UGA codon as selenocysteine (Sec). Selenoprotein biosynthesis is inefficient, which may be due to competition between Sec insertion and termination at the UGA/Sec codon. We analyzed the polysome distribution of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA, a member of the glutathione peroxidase family of selenoproteins, in rat hepatoma cell and mouse liver extracts. In linear sucrose gradients, the sedimentation velocity of PHGPx mRNA was impeded compared to CuZn superoxide dismutase (SOD) mRNA, which has a coding region of similar size. Selenium supplementation increased the loading of ribosomes onto PHGPx mRNA, but not CuZn SOD mRNA. To determine whether the slow sedimentation velocity of PHGPx mRNA is due to a block in elongation, we analyzed the polysome distribution of wild-type and mutant mRNAs translated in vitro. Mutation of the UGA/Sec codon to UGU/cysteine increased ribosome loading and protein synthesis. When UGA/Sec was replaced with UAA or when the SECIS element core was deleted, the distribution of the mutant mRNAs was similar to the wild-type mRNA. Addition of SECIS-binding protein SBP2, which is essential for Sec insertion, increased ribosome loading and translation of wild-type PHGPx mRNA, but had no effect on the mutant mRNAs. These results suggest that elongation is impeded at UGA/Sec, and that selenium and SBP2 alleviate this block by promoting Sec incorporation instead of termination.
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PMID:Polysome distribution of phospholipid hydroperoxide glutathione peroxidase mRNA: evidence for a block in elongation at the UGA/selenocysteine codon. 1110 57

Mice inoculated with hepatoma cell (H22) suspension subcutaneously at their right axilla were administered orally with kappa-selenocarrageenan (Se) solution, the inoculated hepatoma's growth was suppressed. Different concentrations of Se solution added in human hepatoma cell line culture could inhibit proliferation and induce apoptosis in hepatoma cells. Meanwhile Se solution could increase the activity of glutathione peroxidase (GSH-Px) in the mice's plasma and the content of NO in the mice's sera and the hepatoma cell culture supernatant as well. Therefore, apoptosis in hepatoma cell induced by Se solution may be associated with the increase in antioxidative activity, the suppression free radical's intervention, and the excessive release of NO by stress.
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PMID:Roles of Se and NO in apoptosis of hepatoma cells. 1120 75

Intravenous administration of tumor necrosis factor-alpha (TNF-alpha) (0.5 microg/mouse) caused hepatocyte apoptosis in BALB/c mice when they were sensitized with D-galactosamine (GalN, 20 mg/mouse). Activation of nuclear factor kappa B (NF-kappa B) and expression of apoptotic Bcl-2 family members were not significantly different between livers of mice treated with TNF-alpha alone and GalN + TNF-alpha, indicating that neither activation of NF-kappa B nor expression of Bcl-2 family is involved in the sensitization by GalN against TNF-alpha-induced hepatocyte apoptosis. To identify differentially expressed genes implicated in GalN-induced hepatocyte sensitization, we adopted mRNA fingerprinting using an arbitrarily primed polymerase chain reaction. The present analysis revealed that mRNA expression of extracellular antioxidant, selenoprotein P, was up-regulated in the livers after GalN administration. GalN-induced increase in its protein level was confirmed by Western blotting. Increased expression of this gene was also observed in the liver of mice treated with concanavalin A, but not anti-Fas antibody. mRNA of another antioxidant, glutathione peroxidase-1, was also up-regulated, and lipid peroxides were produced in the liver after GalN administration. Selenoprotein P mRNA level also increased in Huh-7 human hepatoma cells incubated with GalN (5 or 10 mM). Accordingly, formation of reactive oxygen species (ROS) was observed in GalN-treated Huh-7 cells. H(2)O(2) induced up-regulation of selenoprotein P mRNA and sensitized Huh-7 cells to TNF-alpha-induced apoptosis. These results suggest that ROS produced by GalN may play a pivotal role in hepatocyte sensitization toward TNF-alpha-induced apoptosis.
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PMID:Possible involvement of reactive oxygen species in D-galactosamine-induced sensitization against tumor necrosis factor-alpha-induced hepatocyte apoptosis. 1131 61

The epidermal growth factor (EGF) is a member of the growth factor superfamily that can stimulate the proliferation of many types of cells. Overexpression of EGF receptor (EGFR) was observed in many types of cancer cells. Anti-EGFR antibodies or antisense nucleic acid sequences of EGFR can suppress the growth of hepatoma cells. In order to further investigate the proteome alterations associated with malignant growth of the human hepatoma cells and the influence of EGFR signal pathway on the cellular proteome, we have comparatively analyzed the proteomes of human hepatoma cells transfected with antisense EGFR sequence (cell strain JX-1) and its control cells (cell strain JX-0) by two-dimensional (2-D) gel electrophoresis and mass spectrometry. Image analysis of silver-stained 2-D gels revealed that 40 protein spots showed significant expression changes in JX-1 cells compared to JX-0 cells. Three of them, including the tumor suppressor protein maspin, changed with tendency to the normal levels. Two protein spots were identified as HSP27 in the same gel, and one of them had a reduced level in JX-1 cells. The apparent alterations of HSP27 in expression level might be the results from their differential chemical modifications, suggesting the effect of dynamic post-translational modifications of proteins on the growth of hepatoma cells. Other proteins such as glutathione peroxidase (GPX-1) and 14-3-3-sigma also exhibited altered expression in JX-1 cells, and their functional implications are discussed.
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PMID:Proteome alterations in human hepatoma cells transfected with antisense epidermal growth factor receptor sequence. 1156 94

A novel selenium form, nano red elemental selenium (Nano-Se) was prepared by adding bovine serum albumin to the redox system of selenite and glutathione. Nano-Se has a 7-fold lower acute toxicity than sodium selenite in mice (LD(50) 113 and 15 mg Se/kg body weight respectively). In Se-deficient rat, both Nano-Se and selenite can increase tissue selenium and GPx activity. The biological activities of Nano-Se and selenite were compared in terms of cell proliferation, enzyme induction and protection against free racial-mediated damage in human hepatoma HepG2 cells. Nano-Se and selenite are similarly cell growth inhibited and stimulated synthesis of glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and thioredoxin reductase (TR). When HepG2 cells were co-treated with selenium and glutathione, Nano-Se showed less pro-oxidative effects than selenite, as measured by cell growth. These results demonstrate that Nano-Se has a similar bioavailability in the rat and antioxidant effects on cells.
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PMID:Biological effects of a nano red elemental selenium. 1167 42

Phytoestrogens such as the soy isoflavonoid daidzein have potential health benefits. The antioxidant properties of phytoestrogens are considered to be responsible in part for their protective effects. The antioxidant enzyme (AOE) system plays an important role in the defense of cells against oxidative insults. To determine whether flavonoids can exert antioxidative effects not only directly but also indirectly by modulating the AOE system, we investigated the influence of the flavonoid daidzein on the expression of different AOE. Daidzein treatment of hepatoma H4IIE cells increased catalase mRNA expression two- to threefold. Expression levels of copper zinc superoxide dismutase (CuZnSOD) were not affected by exposure to daidzein. Manganese superoxide dismutase (MnSOD) mRNA expression levels decreased slightly and glutathione peroxidase (GPx) levels increased slightly after daidzein exposure. Changes in AOE mRNA expression levels were significant at 300 micromol/L daidzein. To elucidate the mechanisms underlying the strong increase in catalase mRNA, transfection experiments were performed. Transient transfection of hepatoma cells with reporter plasmids containing different parts of the upstream region of the catalase gene showed a significant one- to threefold increase in reporter gene activity after daidzein exposure. This indicates that daidzein can directly activate the rat catalase promoter region. Despite the increase in catalase mRNA, daidzein pretreatment of cells did not protect against oxidative stress resulting from H(2)O(2) exposure. On the contrary, daidzein itself exerted a mild oxidative stress. In conclusion, the changes in the AOE system provoked by daidzein affected the oxidant rather than the antioxidant properties of daidzein.
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PMID:The phytoestrogen daidzein affects the antioxidant enzyme system of rat hepatoma H4IIE cells. 1188 May 57

Data suggesting that the hepatitis C virus (HCV) core protein influences normal cellular processes remain controversial. To determine the effects of core on cellular gene expression in hepatocytes, we developed a human hepatoma (Huh7)-derived cell line with tightly regulated core expression under the control of a tetracycline-regulated promoter. Cells expressing core did not have impaired proliferative abilities. Changes in gene expression profiles in response to core expression were determined using commercial oligonucleotide microarrays (Affymetrix GeneChip). Significant increases were observed in the abundance of mRNA-encoding members of the metallothionein (MT) family, as well as nicotinamide N-methyltransferase (NNMT) and glutathione peroxidase-like protein (GPLP). These changes did not result from removal of tetracycline from growth media, and were confirmed in reverse-transcription polymerase chain reaction (RT-PCR) assays. They suggest that core protein expression leads to intracellular oxidative stress, and that vital cellular functions are, in turn, protected by up-regulation of cellular antioxidant defense mechanisms. In conclusion, these findings can explain many potentially conflicting prior observations concerning the effects of core on cellular physiology, and are of relevance to the role of core protein in the pathogenesis of HCV-related fibrosis and hepatocellular carcinoma.
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PMID:Cellular response to conditional expression of hepatitis C virus core protein in Huh7 cultured human hepatoma cells. 1198 74

After being treated with ascorbic acid (AA) 3 mM + sodium selenite (SS) 1.5 microM, the growth rate and mitotic index of human hepatoma cells BEL-7402 decreased remarkably. The indexes related to cell malignancy were improved, such as cell surface charge obviously decreased, the electrophoresis rate fell from 1.76 microns.s-1.V-1.cm-1 to 0.93, the average of alpha-fetoprotein (alpha-FP) content decreased from 341 micrograms.g-1 protein to 92, and gamma-glutamyl-transpeptidase (gamma-GT) activity from 0.76 U.g-1 protein to 0.19. The indexes related to cell differentiation were affected favourably, such as the level of tyrosine-alpha-ketoglutarate transaminase (TAT) activity increased from 14.2 mumol.g-1 protein to 49.0, and the colonogenic potential decreased 95.3%. These results indicated that hepatoma cells had been successfully induced to redifferentiation by AA + SS. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were significantly higher, while the activity of catalase (CAT) was slower in the treated group than in the control group. The malondialdehyde (MDA) content decreased slightly, reduced glutathione (GSH) decreased sharply, and H2O2 content increased dramatically. In conclusion, these results indicate that the combination of ascorbic acid and sodium selenite may induce the redifferentiation of hepatoma cells and inhibit cell growth by virtue of enhancing the activities of antioxidative enzymes and reducing the formation of H2O2, and altering the cell redox status. The combination of ascorbic acid and sodium selenite may be a potent anticancer treatment option for human hepatoma cells.
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PMID:Effects of ascorbic acid and sodium selenite on growth and redifferentiation in human hepatoma cells and its mechanisms. 1199 48


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