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)

Anti-Fas antibody- and actinomycin D (FA/AD) has been shown to have anti-tumor activity in some tumor cells. However, many of the molecular mechanism of FA/AD-induced apoptosis of human hepatoma Bel-7402 cells have not been fully clarified. In the present study, therefore, the effect of FA/AD in presence or absence of p38MAPK inhibitor SB203580 on the proliferation, apoptosis, p38MAPK, caspase-3, location of p38MAPK and caspase-3, and interaction between p38MAPK and caspase-3 in Bel-7402 cell was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), annexin V-FITC/propidium iodide (PI) double staining, electron microscopy, immunoblot, immunofluorescence and immunoprecipitation/immunoblot assay, respectively. We found that FA/AD significantly resulted in the inhibition of proliferation, induction of apoptosis, activation and up-regulation of p38MAPK, activation and up-regulation of caspase-3, translocation of p38MAPK and caspase-3 from cytosol to nucleus, and formation of p38MAPK/caspase-3 complex in Bel-7402 cells. In contrast, SB203580, a p38MAPK-specific inhibitor, apparently blocked induction of apoptosis, activation and up-regulation of p38MAPK, activation and up-regulation of caspase-3, and translocation of p38MAPK and caspase-3 from cytosol to nucleus in FA/AD-treated Bel-7402 cells. Taken together, we conclude that p38MAPK regulates caspase-3 by binding to caspase-3 in nucleus of Bel-7402 cells during FA/AD-induced apoptosis.
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PMID:P38MAPK regulates caspase-3 by binding to caspase-3 in nucleus of human hepatoma Bel-7402 cells during anti-Fas antibody- and actinomycin D-induced apoptosis. 1864 3

The p53 tumor suppressor gene is the most frequently mutated gene identified in many tumors, including hepatocellular carcinoma (HCC). Gene therapy using the p53 gene has been proposed and performed with inactivation of p53 function. However, there have been few reports of nonviral vector-mediated p53 gene delivery in HCC. In this study, the wild-type p53 (wt-p53) gene was transfected into human hepatocellular carcinoma cell line HepG(2) using the urocanic acid-modified chitosan (UAC) as a nonviral vector, and transfection efficiency was determined by FACS analysis. UAC-mediated p53 transfection in HepG(2) cells resulted in high expression levels of wt-p53 mRNA and protein and significant cellular growth inhibition. DAPI staining and Annexin V/PI double-staining assay revealed apoptosis occurrence in HepG(2) cells after treatment with UAC/pEGFP-p53 complexes. In in vivo studies, intratumoral injection of UAC/pEGFP-p53 complexes into BALB/c nude mice bearing HepG(2) cells clearly suppressed tumor growth, and significantly induced apoptosis. These results demonstrated that UAC-mediated efficient p53 gene transfer could induce apoptosis thereby significantly inhibiting the growth of HepG(2) cells in vitro and in vivo, and suggested that UAC-mediated p53 gene delivery might be a promising approach for HCC gene therapy.
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PMID:Urocanic acid-modified chitosan-mediated p53 gene delivery inducing apoptosis of human hepatocellular carcinoma cell line HepG2 is involved in its antitumor effect in vitro and in vivo. 1892 32

Cytotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, have potential therapeutic activity in tumor therapy. However, the therapeutic effect in solid tumor treatment with CTX III are still largely unknown. In the present study, we investigated whether CTX III affects cell growth and cell cycle progression of hepatocellular carcinoma cell (HepG2). We found that the proliferation of HepG2 cell was inhibited by CTX III, to some extent, in a time- and dose-dependent manner (IC50 2.58microg/ml at 24h). Flow cytometric analysis and annexin V labeling also demonstrated that CTX III increased the percentage of apoptotic cells being associated with cell cycle arrest at S-phase. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot revealed that cyclin D1, cyclin A and cyclin E, which involved in cell apopotosis and cell cycle progression, were down regulated both at transcription and translation levels. CTX III-induced caspase-8, -9 and caspase-3 activation, generation of truncated Bid, releasing of cytochrome c and the change of Bcl-2/Bax ratio on protein and mRNA levels. These findings demonstrated that cyclin D1, cyclin B and cyclin A down-regulation, change of Bcl-2/Bax ratio and caspase-8 and -9 activation contribute to CTX III-induced HepG2 cell apoptosis.
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PMID:Apoptosis of human hepatocellular carcinoma cell (HepG2) induced by cardiotoxin III through S-phase arrest. 1898 2

Hepatocellular carcinoma is one of the most common cancers in the world. Previously, we found that the level of glucocorticoid receptor was significantly higher in hepatocellular carcinoma than in adjacent liver tissues. Moreover, in vitro and in vivo studies showed that glucocorticoid stimulated the growth of hepatoma cells. On the other hand, endogenous metabolites such as 2-methoxyestradiol, a metabolite of estrogen produced in liver, and lactic acid, an end-product of glycolysis can result in apoptosis of tumor cells. There are studies that glucocorticoid inhibited apoptosis induced by different chemotherapeutic drugs, whether glucocorticoid could block endogenous stresses, such as 2-methoxyestradiol- or lactic acid-induced apoptosis in human and murine hepatoma cells is not known. In this study, the antagonistic effects of dexamethasone on 2-methoxyestradiol- and lactic acid-induced apoptosis were investigated in human HepG2 and murine Hepa1-6 hepatoma cells. Treatment of hepatoma cells with 2.5-10 microM 2-methoxyestradiol or 25 mM lactic acid resulted in growth inhibition and decreased viability. In addition, results of cell cycle analysis, annexin V binding assay and DNA fragmentation formation showed that 2-methoxyestradiol- or lactic acid-induced apoptosis of hepatoma cells but these effects were partially blocked by dexamethasone. Combined treatment of hepatoma cells with dexamethasone and 2-methoxyestradiol or lactic acid partially reduced the 2-methoxyestradiol- or lactic acid-induced apoptosis signal. Treatment of hepatoma cells with 2-methoxyestradiol or lactic acid resulted in up-regulation of caspase-8, -9 and -3. Dexamethasone partially suppressed the caspase expression. The Bcl-2 level was induced by dexamethasone treatment but decreased after treatment with 2-methoxyestradiol or lactic acid. These results together suggest that glucocorticoids may protect hepatoma cells from metabolic stress-induced cell damage via anti-apoptotic pathways.
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PMID:Glucocorticoid protects hepatoma cells against metabolic stress-induced cell death. 1902 Jul 60

Hepatitis B virus has been linked to the pathogenesis and carcinogenesis of hepatocellular carcinoma. Components of viruses have been identified within pathological specimens of hepatocellular carcinoma tissue. We characterized the in vitro response of human normal liver cells (L-02 cells) to components of infectious agents related to toll-like receptors. Immortalized human normal liver cells (L-02 cells) exhibited increased proliferation in response to exposure to CpG DNA. This molecule is a well-characterized surrogate for DNA viruses, which are common in the liver. Our experiments show that L-02 cells and some hepatoma cell lines such as HepG2, HuH7, Hep3B, express TLR 9 (CpG-specific). CpG DNA, HBV DNA, DNA of HBV middle envelope protein (MP) containing a number of CpG, supernatant of HepG2.2.15 (HepG2 cells transfected HBV) excreting HBV DNA and extraction of nucleic acids from HepG2.2.15 supernatant can all activate NF-kappaB. In addition, L-02 cells were less susceptible to TNF-alpha-induced apoptosis as measured by Annexin V-FITC staining when stimulated with CpG. mRNA of DNA methyltransferase 1 (DNMT-1) and BCL-2 was increased when L-02 cells were stimulated with CpG DNA. Our study has identified a possible novel mechanism that indicates how CpG DNA of HBV DNA may contribute to the malignant transformation of benign liver cells.
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PMID:Hepatitis B virus DNA-induced carcinogenesis of human normal liver cells by virtue of nonmethylated CpG DNA. 1928 92

Berbamine, a natural compound from the plant Berberis amurensis, is a traditional Chinese medicine mainly used in stimulating normal hematopoiesis in clinic. Our previous studies demonstrated that berbamine has anti-leukemia activity. In this study, we investigated the anticancer activity of berbamine against human hepatocellular carcinoma (HCC) HepG2 cells in vitro and in vivo. Berbamine treatment decreased the cell growth in a dose-dependent manner with an IC(50) value of 34.5 +/- 0.5 microM. Flow cytometric analysis of apoptosis using Annexin V/propidium iodide staining showed that the percentage of apoptotic cells was increased in a time-dependent manner. Berbamine treatment increased the expression level of Fas and P53, caused depolarization of mitochondrial membrane and decrease of membrane potential, and activated caspase-3, -8, and -9 in HepG2 cells. Berbamine-induced apoptosis could be blocked by the broad caspase inhibitor z-VAD-fmk. HepG2 human HCC xenograft mice treated with berbamine showed a significant reduction in tumor growth rates compared to saline-treated mice. These studies suggest that berbamine exerts anticancer effects on human HCC HepG2 cells in vivo and in vitro, the induction of p53 and the activity of the Fas apoptotic system may participate in the anticancer activity of berbamine in HepG2 cells.
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PMID:Berbamine induces Fas-mediated apoptosis in human hepatocellular carcinoma HepG2 cells and inhibits its tumor growth in nude mice. 1940 45

Berberine, an isoquinoline plant alkaloid, has been known to generate a wide variety of biochemical and pharmacological effects. In order to elucidate the molecular mechanism for the berberine-induced enhancement of radio-sensitization, the human hepatoma HepG2 cells were treated with berberine combined with irradiation. The anti-tumor effect of gamma radiation was found to be significantly enhanced by berberine. The evidences of apoptosis, such as apoptotic DNA fragmentation and annexin V staining, were observed in the cells treated with the combination of berberine and irradiation. Additionally, the levels of reactive oxygen species (ROS) and nitric oxide (NO) were apparently elevated in the combination system. The activations of p38, Bax, and caspase-3 were also detected in the irradiated cells pretreated with berberine. The productions of ROS and annexin V staining in the cells treated with the combination of berberine and irradiation were significantly inhibited by the specific inhibitor of p38 MAPK, SB203580. The cell death induced by berberine alone or the combination of berberine and irradiation was suppressed by the anti-oxidant, N-acetyl cysteine (NAC). Taken together, the present results clearly indicate that the combination of berberine and gamma-radiation enhance the anti-cancer effects through the p38 MAPK pathway and ROS generation.
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PMID:The combination of berberine and irradiation enhances anti-cancer effects via activation of p38 MAPK pathway and ROS generation in human hepatoma cells. 1949 7

Hepatoma-derived growth factor (HDGF) is frequently overexpressed in human cancer. The growth factor was previously demonstrated to be a survival factor as knock-down of HDGF suppresses the growth and induces apoptosis in human cancer cells through the Bad-mediated intrinsic apoptotic pathway. However, inactivation of Bad cannot completely repress the apoptosis induced upon HDGF knock-down, indicating the presence of other unidentified pathways. In the present study, HDGF knock-down was shown to trigger the Fas-mediated extrinsic apoptotic pathway in human hepatocellular carcinoma HepG2 cells through NF-kappaB signaling pathway. Increases in Fas expression and fas promoter activity were detected upon HDGF knock-down by Western blot analysis and luciferase reporter assay. Knock-down of fas inhibited HDGF knock-down effect on apoptosis induction and growth suppression as revealed by annexin V binding assay and soft agar assay. Down-regulation of IkappaBalpha was also observed upon HDGF knock-down. Overexpression of IkappaBalpha by transient transfection or inhibition of NF-kappaB by BAY11-7082 suppressed HDGF knock-down effect on fas promoter activation, Fas up-regulation, apoptosis induction and growth suppression. Furthermore, the interaction of Fas-mediated extrinsic and Bad-mediated intrinsic apoptotic pathways was demonstrated as a stronger inhibition on apoptosis induction and growth suppression upon HDGF knock-down was observed when both pathways were inactivated. The results therefore suggested that, through both intrinsic and extrinsic apoptotic pathways, HDGF may function as a survival factor and be a potential target for cancer therapy.
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PMID:Mechanistic study on growth suppression and apoptosis induction by targeting hepatoma-derived growth factor in human hepatocellular carcinoma HepG2 cells. 1971 May 40

The beneficial effects of grape consumption have been attributed to the antioxidant activity of its polyphenols. This study was conducted to investigate the cytoprotective effects of a freeze-dried grape powder (FDGP) on liver cells. FDGP treatment of primary hepatocytes and hepatoma cells revealed increased metabolic activity of cells and phosphorylation of Akt and IkappaBalpha, as well as up-regulation of proliferating cell nuclear antigen (PCNA) level. To study the molecular mechanisms of FDGP effects, cells were treated with TNF-related apoptosis-inducing ligand (TRAIL); taurodeoxycholic acid (TDCA); thapsigargin (TG), to induce cell apoptosis through death receptor-, mitochondria-, or ER-mediated pathway; and H(2)O(2), to induce oxidative stress, respectively. TDCA-induced activation of caspase-3, caspase-7, caspase-9, and Bax was dramatically decreased with cotreatment of FDGP. Furthermore, FDGP reduced levels of annexin V positive cells by 4-fold. Also, FDGP pretreatment restored cellular glutathione content by 71% in cells treated with H(2)O(2). However, FDGP did not inhibit ER-mediated apoptosis. In conclusion, FDGP increased the viability and metabolic activity of liver cells and attenuated oxidative stress- and mitochondria-mediated apoptosis. These data may contribute to the understanding of the mechanisms involved in protective effects of grape in a variety of liver conditions associated with cellular stress.
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PMID:Freeze-dried grape powder attenuates mitochondria- and oxidative stress-mediated apoptosis in liver cells. 1975 44

Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality in Asia. This study evaluated the growth inhibition effect of quercetin and 2-methoxyestradiol in vitro in human HCC cell lines. Combination treatment enhanced the cytotoxic effect in HA22T/VGH and HepG2 cell lines as compared with quercetin or 2-methoxyestradiol alone. The cell population of sub-G0/G1 phase and the level of annexin V binding were increased synergistically after combination treatment with quercetin and 2-methoxyestradiol in both cell lines. Moreover, quercetin combined with 2-methoxyestradiol increased superoxide levels, mitochondrial superoxide dismutase (MnSOD) in mRNA, protein levels, and SOD activity. Finally, we also found the mitochondrial membrane potential was decreased after combination treatment. The changes of reactive oxygen species and mitochondrial disruption were likely to be involved in the mechanism for the synergistic cytotoxicity effects of combination treatment in human hepatoma cells. These results provided a basis for further study of the potential usage of quercetin combination with hormonal agents for the treatment of human hepatoma.
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PMID:Quercetin induces oxidative stress and potentiates the apoptotic action of 2-methoxyestradiol in human hepatoma cells. 1983 48


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