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)

Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5 U/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on s-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC50, 0.02 microM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC50, 0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E3 and 10 E5) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane.
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PMID:Triflavin, an Arg-Gly-Asp containing snake venom peptide, inhibits aggregation of human platelets induced by human hepatoma cell line. 151 27

A decrease in the rate of ATP hydrolysis was observed after preincubation of intact mitochondria from hepatoma 22a with an uncoupler. This effect is due both to a decrease in the rate of ATP transport and to an inactivation of the F0F1-ATPase. The former effect is shown to result from an uncoupler-induced ADP efflux. In de-energized mitochondria from hepatoma (but not from mice liver), the concentration of adenine nucleotides in the matrix equilibrates with the medium concentration via a carboxyatractyloside (CATR)-insensitive transport system. CATR-insensitive accumulation of medium ADP and stoichiometric exchange of added ATP are observed in energized hepatoma mitochondria. The dependence of the uncoupler-induced inactivation of ATPase activity on delta mu H+, pH, and ATP is consistent with the effect being caused by the natural protein inhibitor (IF1) of F0F1. ATP- and pH-dependent inactivation of the enzyme is also observed after disruption of mitochondria with the detergent Lubrol-WX. Almost all F0F1 in hepatoma mitochondria have IF1 bound in a noninhibitory manner. In the presence of uncoupler, this complex converts, via a reversible pH-dependent and an irreversible ATP-dependent process, to an inhibitory complex. The pH-dependent step can be blocked by Zn2+ and Cd2+ ions which probably bind to negatively charged residues on IF1, thereby preventing their protonation and conversion of the protein to an inhibitory conformation.
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PMID:Regulation of ATP hydrolysis in hepatoma 22a mitochondria. 183 36

The effects of Clostridium botulinum C3 ADP-ribosyltransferase and of Clostridium botulinum C2 toxin were studied on the cytoskeleton of rat hepatoma FAO and human glioma U333 cells. After treatment of these cells for 24 to 48 h with C3 (3-30 micrograms/ml), the actin microfilaments disappeared, and the intermediate filament network was found to collapse, while microtubules remained intact. Similar alterations of the cytoskeletal filaments without affecting microtubules were induced by the actin-ADP-ribosylating C2 toxin. In FAO cells, C3 caused the rounding up of cells. Concomitantly, cytosolic 22 to 24 kDa proteins were ADP-ribosylated in a guanine nucleotide-dependent manner. Rounding up of cells and ADP-ribosylation of proteins in intact cells were observed at similar concentration of the transferase. These data suggest a role of the protein substrates of C3 in the regulation of the cytoskeletal integrity.
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PMID:Alteration of the cytoskeleton of mammalian cells cultured in vitro by Clostridium botulinum C2 toxin and C3 ADP-ribosyltransferase. 190 79

A comparative study revealed that Ehrlich ascites carcinoma (EAC) cells use glutamine plus inosine for regeneration of adenylates via the purine nucleotide cycle, whereas AS 30D hepatoma cells use adenosine instead. This observation can be correlated with the very low production of aspartate from glutamine in hepatoma cells. Although glucose is an important energy fuel for EAC, it cannot maintain a high enough level of adenylates unless glutamine is also present. Kinetic analysis of hydrolysis of ATP and ADP in the presence of rotenone suggests that deamination of AMP does not maintain a high enough ATP/ADP ratio and probably does not act as energy buffer after inhibition of cell respiration. It seems that, compared with normal cells, malignant cells have the ability for a very rapid regeneration of adenylates. It is proposed that instability of the adenine nucleotide pool, owing to frequent aerobic-anaerobic transitions, represents an essential feature of neoplasia, with profound impact on the whole metabolism of tumour cells.
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PMID:Mechanism and control of degradation and resynthesis of adenylates in tumour cells. 199 Oct 26

Starting from the assumption that tumor cells constantly experience transient ischemia and anoxia, and that this results in metabolic stress which is reflected above all, on the concentration of ATP, ADP and AMP, in other words, the adenine nucleotide pool (AdN), the aim of our research was to study the degradation and resynthesis kinetics of that pool on two types of malignant cells. All experiments were conducted in vitro with cells of the transplantable tumors of Ehrlich's ascitic carcinoma and the AS 30D hepatoma, and metabolite analyses were carried out enzymatically or by way of the HPLC chromatography method. It was found that immediately after the setting on of anoxia, there comes not only to a fall in ATP, but also to a fall in the complete adenine nucleotide pool for about 50%. The further maintenance of anaerobiosis does not have a significant influence on the AdN pool. The adenine nucleotide pool resynthesis is very rapid in the examined cells, and in the presence of glutamine and inosine, there comes to an occurrence of its significant growth. Evidence is given that the resynthesis in Ehrlich's ascitic carcinoma cells is made possible through the purine nucleotide cycle, which probably brings about the intensive glutamine oxidation and aspartate production, while in the AS 30D hepatoma cells it develops by means of adenosine kinase. The AS 30D hepatoma cells maintain a high ATP level in the absence of oxygen for a long time, provided that iodine-acetate is not added, which points to the fact that they have some other kind of energetic reserve aside from ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Kinetics of degradation and resynthesis of the adenine-nucleotide pool in tumor cells]. 209 81

The cellular mechanism by which the angiotensin II (AII) agonist, Sar1-AII, inhibits production and release of angiotensinogen in human hepatoma HepG2 cells was examined. Pretreatment of HepG2 cells with pertussis toxin attenuated the ability of Sar1-AII to block angiotensinogen production. This effect could be correlated with the in situ ADP-ribosylation of a protein(s) of apparent molecular weight 39,000-41,000 on SDS-PAGE, and attenuation of the ability of Sar1-AII to inhibit cAMP accumulation. The role of cAMP in angiotensinogen production was examined. A transient increase in cAMP accumulation above basal could be evoked by forskolin (8-fold) or by glucagon (5-fold) using insulin-deficient media. Although neither forskolin nor glucagon had a significant effect on angiotensinogen production agents producing a sustained increase in intracellular cAMP (8-bromo-cAMP, dibutyryl-cAMP, cholera toxin) were able to increase angiotensinogen production. Although these data indicate that intracellular cAMP is a regulatory factor in angiotensinogen production other evidence suggests that modulation of intracellular cAMP is not entirely responsible for the effects of Sar1-AII.
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PMID:Involvement of a pertussis toxin-sensitive G protein in the regulation of angiotensinogen production by an angiotensin II analog in HepG2 cells. 217 1

Starvation of Mouse hepatoma cells for essential amino acids or glucose results in the mono-ADP-ribosylation of the 78 kDa glucose-regulated protein, GRP78. Here we show that the ADP-ribosylated and non-ADP-ribosylated forms of GRP78 are interconvertible during tryptophan starvation and refeeding. In addition, the ADP-ribosylation of GRP78 was shown to be reversible even during nutritional stress. The overexpressed pool of non-ADP-ribosylated GRP78 synthesized during tunicamycin treatment was available for ADP-ribosylation during subsequent amino acid starvation, especially in the absence of tunicamycin. The reversible ADP-ribosylation of GRP78 could be part of a metabolic control mechanism in operation during nutritional stress.
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PMID:Reversible ADP-ribosylation of the 78 kDa glucose-regulated protein. 226 6

The reduction of 2,6-dichlorophenolindophenol (DCIP) was measured by amperometric methods in Morris hepatoma 3924A cells, normal isolated rat hepatocytes and in mitochondria isolated from normal rat liver. The influence of aerobic and anaerobic atmospheres and of various inhibitors of cellular metabolism, especially of the respiratory chain (KCN, NaN3, oligomycin), on DCIP-reduction were studied using glucose, succinate, beta-hydroxybutyrate, alpha-keto-glutarate and oxalacetate as substrates. Under the influence of KCN and oligomycin the velocity of DCIP-reduction was increased in both cell types. Azide showed a similar effect on tumour cells and to a lower extent on hepatocytes. Using isolated mitochondria total DCIPred was increased by KCN and azide using various mitochondrial metabolites as substrates and with ADP/Pi present. The effects of KCN, azide and oligomycin could be explained by taking DCIP as an artificial coupling site in mitochondria which is only used when oxygen is absent or when the respiratory chain is blocked by inhibitors of cytochrome oxidase. Evaluation of the reaction kinetics revealed differences between normal and transformed cells in terms of the pseudo-first-order rate constants and the activity of overall oxidoreductases. The results apparently reflect quantitative differences in enzymatic equipment and the metabolic pathways predominating in normal and neoplastic cells.
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PMID:Investigation by amperometric methods of intracellular reduction of 2,6-dichlorophenolindophenol in normal and transformed hepatocytes in the presence of different inhibitors of cellular metabolism. 229 12

Our previous studies have demonstrated that 3-aminobenzamide (3AB), an inhibitor of adenosine diphosphate-ribosyl transferase (ADPRT) could enhance the cytotoxicity (in vitro) and antitumor activity (in vivo) of bleomycin (BLM) A5 and peplomycin (PEP) against S-180, hepatoma and Ehrlich ascites carcinoma (EAC). In this study, it was shown that the inhibition rates (INR's) of S-180 in two experiments were increased from 42.5 and 46.1% to 66.2 and 75.9% when BLM 2.5 mg/kg/day x 8 was combined with 3AB 385.4 mg/kg/day x 8, while the decrease of body weight could not be enhanced. BLM at a dose of 5 mg/kg/day x 8 gave INR's of 64.8 and 75%, similar to the combined group but decreased the body weight more significantly. However, the addition of 3AB 385.4 mg/kg/day to BLM did not increase the acute toxicity of BLM alone. There was no significant difference of change of the body weight and subacute toxicity between the BLM and BLM + 3AB group. There was no difference of peripheral blood white cell count and the pathomorphological and ultrastructural change, wet weight and hydroxyproline content (to reflect the collagen content) of the lung of the mice between BLM alone and BLM + 3AB group. Therefore, the study provided experimental evidences for the reasonable use of nontoxic ADPRT inhibitors in adjunct to the chemotherapy of BLM in cancers.
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PMID:The potentiation of the antitumor activity but not toxicity of bleomycin by 3-aminobenzamide. 248 41

The O6-methylguanine-DNA-methyltransferase (transferase) activity in a rat hepatoma cell line (H4 cells) is enhanced as a response to DNA damaging agents. To study whether poly (ADP-ribosylation) is involved in this induction, the cells were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) that induces the transferase activity and stimulates poly (ADP-ribose) synthesis. Addition of poly (ADP-ribose) polymerase inhibitors enhanced the transferase increase induced by MNNG. The influence of the inhibitors on the transferase induction was dose and time-dependent. The results suggest that poly (ADP-ribose) is involved in the induction of this protein.
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PMID:Potentiation of N-methyl-N'-nitro-N-nitrosoguanidine-induced O6-methylguanine-DNA-methyltransferase activity in a rat hepatoma cell line by poly (ADP-ribose) synthesis inhibitors. 250 71


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