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)

Bullatacin, a potential antitumor Annonaceous acetogenin (AA), is isolated from the seed of the Formosa Annona atemoya. We reported previously that bullatacin inhibits the secretion of hepatitis B surface antigen from 2.2.15 cells (human hepatoma HepG2 cells transfected with hepatitis B virus DNA plasmid). In the present study, we determined cell apoptosis by using double-dye staining with fluorescein-isothiocyanate-labeled annexin V and propidium iodide. We found that bullatacin induced apoptosis in 2.2.15 cells in a time-dependent manner; the most significant apoptotic change appeared at 16 hr. Moreover, different concentrations (10(-3) to 1.0 microM) of bullatacin induced apoptosis in a concentration-dependent manner at 16 hr. The determination of intracellular cyclic AMP (cAMP) and cyclic GMP (cGMP) levels in 2.2.15 cells after exposure to bullatacin demonstrated that bullatacin caused both to decrease in a time- and concentration-dependent manner. A time course (0.33, 1, 6, 16, 24hr) study indicated that while both cAMP and cGMP levels decreased early (at 0.33 hr), the most dramatic decline appeared at 6 hr. Meanwhile, the inhibitory effect on cAMP and cGMP levels reached a maximum at 16 hr (90.5+/-3.2 and 47.3+/-12.8%, respectively). The concentration-dependent decrease of both cAMP and cGMP induced by bullatacin was parallel with the magnitude of apoptosis induced by various concentrations (10(-3) to 1.0 microM) of bullatacin. Additionally, the bullatacin-induced apoptosis was inhibited by the addition of cAMP and cGMP elevating agents (forskolin and S-nitrosoglutathione). Our results suggest that a decrease of both cAMP and cGMP levels may play a crucial role in bullatacin-induced apoptosis in 2.2.15 cells.
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PMID:Bullatacin, a potent antitumor Annonaceous acetogenin, induces apoptosis through a reduction of intracellular cAMP and cGMP levels in human hepatoma 2.2.15 cells. 1252 25

Long-dan-tan (Chinese name) is one of the most common herbal medicines used by Chinese people with chronic liver disease. Accumulated anecdotal evidence suggests that Long-dan-tan may show a beneficial effect in patients with hepatocellular carcinoma. Long-dan-tan is made from five plants: Gentiana root, Scutellaria root, Gardenia fruit, Alisma rhizome, and Bupleurum root. In this study, we have examined the cytotoxic effects of the five major ingredients isolated from the above plants, i.e. gentiopicroside, baicalein, geniposide, alisol B acetate and saikosaponin-d, respectively, on human hepatoma Hep3B cells. Annexin V immunofluorescence detection, DNA fragmentation assays and FACScan analysis of propidium iodide-staining cells showed that gentiopicroside, baicalein, and geniposide had little effect, whereas alisol B acetate and saikosaponin-d profoundly induced apoptosis in Hep3B cells. Alisol B acetate, but not saikosaponin-d, induced G2/M arrest of the cell cycle as well as a significant increase in caspase-3 activity. Interestingly, baicalein by itself induced an increase in H(2)O(2) generation and the subsequent NF-kappaB activation; furthermore, it effectively inhibited the transforming growth factor-beta(1) (TGF-beta(1))-induced caspase-3 activation and cell apoptosis. We suggest that alisol B acetate and saikosaponin-d induced cell apoptosis through the caspase-3-dependent and -independent pathways, respectively. Instead of inducing apoptosis, baicalein inhibits TGF-beta(1)-induced apoptosis via increase in cellular H(2)O(2) formation and NF-kappaB activation in human hepatoma Hep3B cells.
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PMID:Pharmacological evaluation of several major ingredients of Chinese herbal medicines in human hepatoma Hep3B cells. 1290 91

We have already reported that serum levels of soluble Fas (sFas) and Fas-positive mononuclear cells increased concomitantly with deterioration in renal function and the increases were statistically significant. Moreover, the severity of renal anemia in renal failure patients was significantly correlated with serum levels of sFas. Therefore, we investigated whether or not Fas and Fas ligand (FasL) influenced the production of erythropoietin (EPO). Hep G2 cells, an EPO productive human hepatocellular carcinoma cell line, were cultured in MEM medium with 10% of FCS containing 1, 10 or 100 ng/ml of sFas, or sFasL. The EPO concentrations of the supernatants were measured by the ELISA method, Annexin V positive cells were calculated by flow cytometry, H3 leucin uptake was measured by a liquid scintillation counter, an MTT assay was performed using the light absorption method, fragmented nuclei were stained by the TUNEL method and DNA laddering was observed by agarose gel electrophoresis. Their characteristics evaluated at 0, 24, 48 and 72 hrs. Both EPO production and H3 leucin uptake were suppressed in culture with sFas or sFasL, dose-dependently and declines in MTT activities accompanied these changes at 24 hrs. In addition, nuclear fragmentation and DNA laddering were found to be stimulated in culture with sFas or sFasL at 48 hrs. These data suggest that sFas induced apoptosis and had a cytotoxic effect on Hep G2 cells. In conclusion, hyper-sFas-emia observed in chronic renal failure may regulate the production of EPO, which indicates that sFas acts as a uremic toxin.
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PMID:[Investigation of the influence of Fas antigen on Hep G2 cells, an erythropoietin producing cell line]. 1463 62

The aim of the present study was to investigate in vitro the mechanism of toxicity of isoniazid (= INH), the drug most widely used for treatment of tuberculosis. The human hepatoma line HepG2, the human lymphoblastoid line AHH-1 and the murine lymphoma cells YAC-1 were used as test systems. Active cell death (= apoptosis) and necrosis were detected by different flow cytometric methods: the binding of annexin V to the cell membrane and staining with propidium iodide (PI), the TUNEL assay for detection of DNA fragmentation and the occurrence of a sub G1 peak in cell cycle histograms. Mitochondrial membrane potential was analysed with the fluorescent probe JC-1. In addition to cytotoxicity, effects of INH on cell cycle were studied in HepG2 cells. The data of the present investigations indicate that INH induces cytotoxicity via apoptosis both in hepatoma and lymphoma cells. Twenty-four hours of application of INH in concentrations > 26 mM led to a remarkable number of apoptotic cells positive for Annexin V. The induction of apoptosis was accompanied by a break down of the mitochondrial membrane potential and the occurrence of DNA strand breaks. At incubation times from 36 to 48 hours, a sub-G1 peak of late apoptotic cells was detected in cell cycle analysis. Furthermore, cell cycle studies showed a disruption of the cycle at low concentrations of INH which are only mildly cytotoxic. Thus the present study unequivocally demonstrated that INH induces cytotoxicity via apoptosis and can lead to a significant disturbance of the cell cycle in mammalian cells.
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PMID:In vitro studies on the toxicity of isoniazid in different cell lines. 1468 83

The objective of this study was to investigate the effects of Gelidium amansii, an edible red agar cultivated off the northeast coast of Taiwan, on the growth of two lines of cancer cells, murine hepatoma (Hepa-1) and human leukemia (HL-60) cells, as well as a normal cell line, murine embryo fibroblast cells (NIH-3T3). The potential role of G. amansii on the induction of apoptosis was also examined. The results indicated that all extracts from G. amansii, including phosphate-buffered saline (PBS) and methanol extracts from dried algae as well as the dimethyl sulfoxide (DMSO) extract from freeze-dried G. amansii agar, inhibited the growth of Hepa-1 and NIH-3T3 cells, but not the growth of HL-60 cells. Annexin V-positive cells were observed in methanol and DMSO extract-treated, but not PBS extract-treated Hepa-1 and NIH-3T3 cells, suggesting that the lipid-soluble extracts of G. amansii induced apoptosis. In summary, extracts of G. amansii from various preparations exhibited antiproliferative effects on Hepa-1 and NIH-3T3 cells, and apoptosis may play a role in the methanol and DMSO extract-induced inhibitory effects. However, the antiproliferative effects of PBS extracts was not through apoptosis. Moreover, the growth-inhibitory effects of G. amansii were not specific to cancer cells.
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PMID:Growth-inhibitory effects of the red alga Gelidium amansii on cultured cells. 1475 29

Irradiation of murine hepatoma 1c1c7 cultures presensitized with N-aspartyl chlorin e6 (NPe6) caused lysosomal disruption and apoptosis. Tao cells, a variant of the 1c1c7 line having lower aryl hydrocarbon receptor (AhR) contents, were resistant to the pro-apoptotic effects of NPe6 in the same photodynamic therapy protocol. Colony-forming assays were used to establish light dose-dependent and NPe6 concentration-dependent cytotoxicity curves. Lysosomal breakage and cell survival paralleled one another in both cell types. When analyzed at comparable lethal dose conditions, the onset of apoptosis was delayed, and the magnitude of the apoptotic response was muted in Tao cells, as assessed by morphology, annexin V binding, caspase-3 activities, and analyses of Bid, procaspase-9, and pro-caspase-3 cleavage. In contrast, the kinetics/magnitude of pro-caspase-3 activation in the two cell lines were identical after exposure to HA14 -1 or Jo2 antibody, inducers of the intrinsic and extrinsic apoptotic pathways, respectively. Tao endosomal/lysosomal extracts contained approximately 50%, 35%, and 55% of the Bid cleavage and cathepsin B and D activities of 1c1c7 endosomes/lysosomes, respectively. Western blot analyses confirmed reduced cathepsin B/D contents in Tao cells. Analyses of 1c1c7/Tao variants engineered to express antisense/sense AhR constructs suggested that endosomal/lysosomal cathepsin B and D content, but not whole cell content, correlated with AhR expression. These studies provide a mechanism for the resistance of Tao cultures to the proapoptotic effects of a protocol causing targeted disruption of lysosomes. They also suggest that the AhR, in the absence of exogenous ligand, may affect the trafficking/processing of proteases normally found in endosomes/lysosomes.
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PMID:Differential susceptibilities of murine hepatoma 1c1c7 and Tao cells to the lysosomal photosensitizer NPe6: influence of aryl hydrocarbon receptor on lysosomal fragility and protease contents. 1504 32

Acetaminophen in large doses is well-known as hepatotoxic, and early therapy with N-acetylcysteine is frequently life-saving. However, in later stages of acetaminophen poisoning, treatment with N-acetylcysteine is not always effective. Although some of the pathways of acetaminophen toxicity and the effect of N-acetylcysteine have been elucidated, in depth information on this process is still lacking. Hepatoma-derived HepG2 cultured cells were exposed to acetaminophen (5 and 10 mM), with or without N-acetylcysteine (5 mM), for 24 and 48 hr. For the assessment of oxidative damage, apoptosis and necrosis, we followed redox status, glutathione content, nuclear fragmentation, phosphatidylserine externalization and ultrastructural changes. Variations in Ca2+ level and number of mitochondrial dense granules were also studied. Acetaminophen treatment of HepG2 cells caused oxidative damage and apoptosis. Significant decrease of cellular redox potential and glutathione content were time- and concentration-dependent. The protective effect of N-acetylcysteine was expressed by an increase of intracellular glutathione and of the level of metabolic reduction of the redox indicator Alamar Blue. The apoptogenic effect of acetaminophen was assessed by flow cytometry of annexin V binding, nuclear hypodiploidity, intracellular Ca2+, as well as by ultrastructural examination. Beyond 24 hr of acetaminophen exposure, necrosis was also noticed. We conclude that acetaminophen-induced oxidative damage in HepG2 cultured cells can be prevented by exposure to N-acetylcysteine. However, apoptosis, either early or late, here demonstrated, is not avoided by exposure to N-acetylcysteine. N-Acetylcysteine did not prevent acetaminophen-induced plasma membrane asymmetry, nuclear damage, alterations of Ca2+ homeostasis and ultrastructural changes.
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PMID:N-acetylcysteine does not protect HepG2 cells against acetaminophen-induced apoptosis. 1512 91

Parvovirus B19 (B19 virus) can persist in multiple tissues and has been implicated in a variety of diseases, including acute fulminant liver failure. The mechanism by which B19 virus induces liver failure remains unknown. Hepatocytes are nonpermissive for B19 virus replication. We previously reported that acute fulminant liver failure associated with B19 virus infection was characterized by hepatocellular dropout. We inoculated both primary hepatocytes and the hepatocellular carcinoma cell line Hep G2 with B19 virus and assayed for apoptosis by using annexin V staining. Reverse transcriptase PCR analysis and immunofluorescence demonstrated that B19 virus was able to infect the cells and produce its nonstructural protein but little or no structural capsid protein. Infection with B19 virus induced means of 28% of Hep G2 cells and 10% of primary hepatocytes to undergo apoptosis, which were four- and threefold increases, respectively, over background levels. Analysis of caspase involvement showed that B19 virus-inoculated cultures had a significant increase in the number of cells with active caspase 3. Inhibition studies demonstrated that caspases 3 and 9, but not caspase 8, are required for B19 virus-induced apoptosis.
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PMID:Parvovirus B19-induced apoptosis of hepatocytes. 1522 Apr 51

Since hepatocellular carcinoma remains a major challenging clinical problem in many parts of the world including Eastern Asia and Southern Africa, it is imperative to develop more effective chemopreventive and chemotherapy agents. Herein, we present an investigation regarding the anticancer potential of luteolin, a natural flavonoid, and the mechanism of its action in human hepatoma HepG2 cells. Using DNA fragmentation assay and nuclear staining assay, it showed that luteolin induced apoptosis of HepG2 cells. Luteolin induced the cytosolic release of cytochrome c and activated CPP32. We found that Bax and Bak translocated to mitochondria apparently, whereas Fas ligand (FasL) was unchanged after a treatment with luteolin for 3 h. In addition, it showed that c-Jun NH2-terminal kinase (JNK) was activated after the treatment of luteolin for 3-12 h. Further investigation showed that a specific JNK inhibitor, SP600125, reduced the activation of CPP 32, the mitochondrial translocation of Bax, as well as the cytosolic release of cytochrome c that induced by luteolin. Finally, the apoptosis induced by luteolin was suppressed by a pretreatment with SP600125 via evaluating annexin V-FITC binding assay. These data suggest that luteolin induced apoptosis via mechanisms involving mitochondria translocation of Bax/Bak and activation of JNK.
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PMID:Induction apoptosis of luteolin in human hepatoma HepG2 cells involving mitochondria translocation of Bax/Bak and activation of JNK. 1571 Jan 73

A decoction of Nigella sativa seeds, Hemidesmus indicus root and Smilax glabra rhizome is used by traditional medical practitioners in Sri Lanka to treat cancer and has been shown to prevent chemically induced carcinogenesis in rats. The cytotoxicity of the decoction and the individual plant extracts were tested on the human hepatoma HepG2 cell line. The effects of 24 h incubation with different concentrations (0--50 mg/ml) of the extracts on HepG2 cells were determined. Results from MTT and SRB assays, and [(14)C]-leucine and [(3)H]-thymidine uptake demonstrated that the decoction had a strong dose-dependent cytotoxic activity. The greatest inhibitory effects were observed on DNA synthesis with both the decoction (91+/-S.E. 3.7% inhibition) and N. sativa plant extract (88+/-3.8%) even at low concentrations (5 mg/ml). The three individual plant extracts were cytotoxic in the order of potency N. sativa>H. indicus>S. glabra. Flow cytometric analysis using Annexin V and propidium iodide staining showed that after 24 h exposure to the decoction, cells were in the late stage of apoptosis and/or necrosis. Further experiments are worthwhile to determine the anticancer potential of this plant decoction and its components.
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PMID:Cytotoxic effects of a decoction of Nigella sativa, Hemidesmus indicus and Smilax glabra on human hepatoma HepG2 cells. 1591 74


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