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)

Both experimental and epidemiologic studies have linked a low dietary intake of selenium with an increased risk of cancer. The authors examined the association between plasma selenium levels and risk of hepatocellular carcinoma (HCC) among chronic carriers of hepatitis B and/or C virus in a cohort of 7,342 men in Taiwan who were recruited by personal interview and blood draw during 1988-1992. After these men were followed up for an average of 5.3 years, selenium levels in the stored plasma were measured by using hydride atomic absorption spectrometry for 69 incident HCC cases who were positive for hepatitis B surface antigen (HBsAg) and/or antibodies against hepatitis C virus (mostly HBsAg positive) and 139 matched, healthy controls who were HBsAg positive. Mean selenium levels were significantly lower in the HCC cases than in the HBsAg-positive controls (p = 0.01). Adjusted odds ratios of HCC for subjects in increasing quintiles of plasma selenium were 1.00, 0.52, 0.32, 0.19, and 0.62, respectively. The inverse association between plasma selenium levels and HCC was most striking among cigarette smokers and among subjects with low plasma levels of retinol or various carotenoids. There was no clear evidence for an interaction between selenium and alpha-tocopherol in relation to HCC risk.
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PMID:Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. 1045 13

T-2 toxin is a secondary fungal metabolite produced by various species of Fusarium. It is capable of killing cells by causing extensive damage to the cellular membrane. In this study, cytotoxicity of T-2 toxin in combination with different antioxidant materials, including vitamin C (vit. C), vitamin E (vit. E) and selenium (sel) was investigated in vitro using the neutral red cytotoxicity assay. Eleven primary and transformed cell lines established from different tissues were used in pre-test experiments to identify the most sensitive and resistant lines by measuring the half lethal concentration (LC(50)) of the toxin. Three cell lines including human gingival fibroblast (HGF), the most sensitive (LC(50)=0.25 ng/ml), human colorectal adenocarcinoma (SW742), the most resistant (LC(50)=5.5 ng/ml) and human hepatoma (HepG2), with median susceptibility (LC(50)=2 ng/ml) were selected to investigate the inhibitory effects of the antioxidant agents, on cytotoxicity of T-2 toxin. Our results demonstrated that co-incubation of cell lines with different concentrations of T-2 toxin and antioxidants decreased significantly, but did not totally inhibit, the cytotoxicity of T-2 toxin (P<0.001). These findings suggest that in addition to lipid peroxidation, which is inhibited by antioxidants, other unidentified mechanism(s) seem to be involved in cytotoxicity of T-2 toxin.
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PMID:In vitro inhibitory effects of antioxidants on cytotoxicity of T-2 toxin. 1081 49

It is well known that glutathione, the major intracellular antioxidant, is closely involved in the metabolism and bioactivity of selenium. In the present study, glutathione was demonstrated to play a dual role on selenite (Se)-induced oxidative stress and apoptosis in human hepatoma HepG(2) cells. The experiment was carried out in two different modes to modulate intracellular reduced glutathione (GSH) content. In Mode A (pretreatment), cells were pretreated with N-acetylcysteine (NAC), buthionine sulfoximine (BSO), or GSH prior to Se exposure. In Mode B (simultaneous treatment), cells were treated with Se and NAC, BSO, or GSH simultaneously. It was found that Se-induced oxidative stress and apoptosis are closely related to the intracellular level of GSH. Both the increase and depletion of GSH content significantly enhanced Se-induced oxidative stress and apoptosis in HepG(2) cells. Results from this study clearly demonstrated that GSH has a dual role in the effects of Se on cancer cells: (i) GSH acts as a pro-oxidant, facilitating Se-induced oxidative stress, and (ii) GSH acts as an antioxidant, protecting against Se-induced oxidative stress and apoptosis. Understanding such a unique association between GSH and Se may help to explain the controversy in the literature over the complex relationship between selenium and glutathione, and ultimately the capability of selenium to prevent cancer.
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PMID:Dual role of glutathione in selenite-induced oxidative stress and apoptosis in human hepatoma cells. 1083 73

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

Selenium has been implicated in cancer prevention, but the mechanism and possible involvement of selenoproteins in this process are not understood. To elucidate whether the 15-kDa selenoprotein may play a role in cancer etiology, the complete sequence of the human 15-kDa protein gene was determined, and various characteristics associated with expression of the protein were examined in normal and malignant cells and tissues. The 51-kilobase pair gene for the 15-kDa selenoprotein consisted of five exons and four introns and was localized on chromosome 1p31, a genetic locus commonly mutated or deleted in human cancers. Two stem-loop structures resembling selenocysteine insertion sequence elements were identified in the 3'-untranslated region of the gene, and only one of these was functional. Two alleles in the human 15-kDa protein gene were identified that differed by two single nucleotide polymorphic sites that occurred within the selenocysteine insertion sequence-like structures. These 3'-untranslated region polymorphisms resulted in changes in selenocysteine incorporation into protein and responded differently to selenium supplementation. Human and mouse 15-kDa selenoprotein genes manifested the highest level of expression in prostate, liver, kidney, testis, and brain, and the level of the selenoprotein was reduced substantially in a malignant prostate cell line and in hepatocarcinoma. The expression pattern of the 15-kDa protein in normal and malignant tissues, the occurrence of polymorphisms associated with protein expression, the role of selenium in differential regulation of polymorphisms, and the chromosomal location of the gene may be relevant to a role of this protein in cancer.
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PMID:Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology. 1094 81

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

We have studied the relationship between antioxidant and anticancer properties of selenium (Se) in multistage hepatocarcinogenesis induced by N-nitrosodiethylamine (DEN). In this study we have observed an increased level of lipid peroxide (LPO) products and decreased antioxidant enzyme activities (superoxide dismutase and catalase) in hepatoma and surrounding liver tissues of cancer-bearing animals. Selenium (Se) was supplemented either before initiation or during initiation and selection/promotion phases of hepatocarcinogenesis and was found to be effective in altering hepatic lipid peroxidation and antioxidant enzyme activities to a statistically significant level measured either in the hepatoma or in the surrounding liver tissues. These alterations inclined towards normal in a time-dependent manner on selenium supplementation. Furthermore, increased levels of lipid peroxidation and decreased levels of antioxidants (superoxide dismutase and catalase) were also observed in distant organs of cancer-bearing rats other than the tumour-bearing site. These alterations are brought back to normal levels upon Se treatment. Our results confirm the fact that Se is particularly protective in limiting the action of DEN by its antioxidant property.
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PMID:Effect of selenium on N-nitrosodiethylamine-induced multistage hepatocarcinogenesis with reference to lipid peroxidation and enzymic antioxidants. 1122 68

Mortality from hepatocellular carcinoma (HCC) is extraordinarily high in Matzu, an island off the coast of Southeastern China. To investigate factors associated with plasma aflatoxin B1 (AFB1)-albumin adduct level, we studied 304 healthy adult residents from Matzu. AFB1-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen status by enzyme immunoassay, genotypes of glutathione S-transferase (GST) M1 and T1 by polymerase chain reaction, plasma selenium by atomic absorption spectrometry, and plasma retinol, alpha-tocopherol, alpha-carotene, and beta-carotene levels by high-performance liquid chromatography. Men had higher AFB1-albumin adduct levels than women. GSTM1-nonnull and GSTT1-null genotypes and low plasma selenium level were significantly associated with an increased level of AFB1-albumin adducts among men, whereas age was significantly correlated with adduct level among women. High intake of fermented beans was associated with an increased adduct level among men and women. The inverse associations between plasma selenium level and AFB1-albumin adducts were statistically significant among those with null genotypes of GSTM1 and GSTT1, but not among the nonnull genotypes. This study provides insight into the dietary and genetic factors influencing AFB1-albumin adduct formation in an isolated population with high liver cancer mortality.
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PMID:Associations of plasma aflatoxin B1-albumin adduct level with plasma selenium level and genetic polymorphisms of glutathione S-transferase M1 and T1. 1152 95

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

The chemopreventive/chemotherapeutic effect of sodium selenite on tricarboxylic acid cycle key enzymes was investigated against hepatoma induced by environmental carcinogen N-nitrosodiethylamine. Decreased activities of TCA cycle key enzymes such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) in hepatoma and surrounding tissues of hepatoma-bearing rats were observed. Upon selenium supplementation the above biochemical changes were reverted in a dose- and duration-dependent manner. This study further confirms the chemopreventive/chemotherapeutic effect of sodium selenite which is found to be more effective in the initiation phase of carcinogenesis.
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PMID:Chemopreventive efficacy of selenium against N-nitrosodiethylamine-induced hepatoma in albino rats. 1174 7


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