Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paeonol, a major phenolic component of Moutan Cortex, is known to have antitumor effects through an unknown mechanism. In this study, we tried to elucidate the anticancer effects of paeonol on human hepatocellular carcinoma (HCC) cell lines BEL-7404, SMMC-7721, and MHCC97-H in vitro. Using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, we compared the cytotoxicity of paeonol with the cytotoxicity of 5-fluorouracil (5-FU) in these three HCC cell lines. In addition, we examined the combined effect of paeonol and 5-FU over time, and found that the two compounds inhibited the proliferation of all three human HCC cell lines in a dose-dependent manner. The concentrations that inhibited the proliferation by 50% ranged from 11.39 to 56.23 mg/l for paeonol, and 6.47 to 37.87 mg/l for 5-FU. We determined that exposure to these compounds led to an upregulation of the anti-oncogene PTEN, and the downregulation of the oncogene AKT in the cell lines tested as determined by real-time quantitative reverse transcription-PCR and western blot. In addition, paeonol induced DNA fragmentation in the HCC cell line BEL-7404. These observations suggest that paeonol has the potential to be explored for use as an effective antitumor agent for HCC.
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PMID:Antiproliferative and apoptotic effects of paeonol on human hepatocellular carcinoma cells. 1845 50

Vitamin K2 [menaquinone-4 (MK-4)] has been reported to induce apoptosis in hepatocellular carcinoma, leukemia, and MDS cell lines. The effects of MK-4 on the development of arthritis have never been addressed so far. In this study, we investigated the effect of MK-4 upon the proliferation of rheumatoid synovial cells and the development of arthritis in collagen-induced arthritis (CIA). We analyzed the effect of MK-4 on the proliferation of fibroblast-like synoviocytes (FLSs) using the 3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The proapoptotic effect of MK-4 upon FLS was investigated with annexin V staining and DNA fragmentation and caspase 3/7 assays. Moreover, we analyzed the effect of MK-4 on the development of CIA in female dark agouti rats. Our results indicated that MK-4 inhibited the proliferation of FLS and the development of CIA in a dose-dependent manner. We concluded that MK-4 may represent a new agent for the treatment of RA in the setting of combination therapy with other disease-modifying antirheumatic drugs.
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PMID:Vitamin K and rheumatoid arthritis. 1848 89

Five new type binuclear platinum(II) complexes (a-e) have been synthesized and characterized by elemental analysis, conductivity, thermal analysis, IR, UV, (1)H NMR and mass spectral techniques. The cytotoxicity of the complexes was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The acute toxicity and antitumor activity of complex ein vivo were also studied. The results indicate that complexes a-d have no activity against HL-60, MCF-7, BGC-823, EJ and HCT-8 cell lines, with a higher IC(50) value (>50 microM). Complex e confers substantially greater cytotoxicity against HL-60, MCF-7, BGC-823, EJ and HCT-8 cell lines with an IC(50) value of 0.02+/-0.009, 1.70+/-0.21, 4.00+/-0.35, 0.98+/-0.02 and 1.02+/-0.21 microM, respectively. LD(50) of complex e is 815.3mg/kg, it was significantly higher than that of cisplatin and carboplatin. Complex e at dose of 4, 12 and 20mg/kg has no activity against mouse hepatocarcinoma H22 and Lewis lung carcinoma in mice, but displays significant activity against human ovarian carcinoma A2780 and human colon carcinoma HCT-116 in nude mice at dose of 12 mg/kg, and activity is similar to that of cisplatin at dose of 4 mg/kg. Complex e at dose of 20mg/kg has no activity against human lung adenocarcinoma A549 in nude mice (P>0.05). The results suggest that the species of amine for the new type binuclear platinum complexes have important effect on their cytotoxicity, and they may be a new class platinum anticancer drugs.
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PMID:Synthesis, characterization and antitumor activity of new type binuclear platinum(II) complexes. 1852 22

Identifying changes at the molecular level during the development of hepatocellular carcinoma is important for the detection and treatment of the disease. The characteristic structural reorganization of preneoplastic cells may involve changes in the microtubule cytoskeleton. Microtubules are dynamic protein polymers that play an essential role in cell division, maintenance of cell shape, vesicle transport, and motility. They are comprised of multiple isotypes of alpha- and beta-tubulin. Changes in the levels of these isotypes may affect not only microtubule stability and sensitivity to drugs but also interactions with endogenous proteins. We employed a rat liver cancer model that progresses through stages similar to those of human liver cancer, including metastasis to the lung, to identify changes in the tubulin cytoskeleton during carcinogenesis. Tubulin isotypes in both liver and lung tissue were purified and subsequently separated by isoelectric focusing electrophoresis. The C-terminal isotype-defining region from each tubulin was obtained by cyanogen bromide cleavage and identified by mass spectrometry. A novel post-translational modification of betaIVb-tubulin in which two hydrophobic residues are proteolyzed from the C-terminus, thus exposing a charged glutamic acid residue, was identified. The unique form of betaIVb-tubulin was quantified in the liver tissue of all carcinoma stages and found to be approximately 3-fold more abundant in nodular and tumor tissue than in control tissue. The level of this form was also found to be increased in lung tissue with liver metastasis. This modification alters the C-terminal domain of one of the most abundant beta-tubulin isotypes in the liver and therefore may affect the interactions of microtubules with endogenous proteins.
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PMID:Increased levels of a unique post-translationally modified betaIVb-tubulin isotype in liver cancer. 1857 Mar 81

Propiconazole is a triazole-containing fungicide that is used agriculturally on grasses, fruits, grains, seeds, hardwoods, and conifers. Propiconazole is a mouse liver hepatotoxicant and a hepatocarcinogen that has adverse reproductive and developmental toxicities in experimental animals. The goal of this study was to investigate the cytotoxic responses of propiconazole and its metabolites to determine if metabolism of this agent differentially affected its cytotoxic activities in hepatic tumor cell lines and in primary hepatocytes. To this end the cytotoxic effects of propiconazole and five of its metabolites were examined in three hepatic cell types: The mouse hepatoma Hepa1c1c7 cell line, the human hepatoma HepG2 cell line, and primary cultures of mouse hepatocytes. We initially compared the responses of propiconazole exposure in both Hepa1c1c7 and HepG2 cell lines over a concentration range of 0-200 microM using two assay systems: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the neutral red assay. Concentration-related cytotoxic responses were evident in both cell lines using both endpoints with the MTT assay providing enhanced sensitivity. The relative cytotoxic effects of propiconazole and five propiconazole metabolites were further assessed by the MTT assay using Hepa1c1c7 and HepG2 tumor cell lines. The cell cultures were exposed to various concentrations of propiconazole and five of its metabolites over a range of 0-400 microM. Propiconazole was cytotoxic in both cell lines in a dose-dependent manner. All five metabolites were less cytotoxic in both cell lines compared to the parent compound. The most cytotoxic metabolites in Hepa1c1c7 and HepG2 cells among the five were 3-(2-((1H-1,2,4-triazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)propan-1-ol and 1-(2-((1H-1,2,4-triazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)propan-2-ol. Propiconazole was cytotoxic in primary mouse hepatocytes; however none of the five propiconazole metabolites exerted cytotoxic activities. There was a linear relationship between the cLogP and the cytotoxic effects of propiconazole and its five metabolites in Hepa1c1c7 cells. We conclude that these propiconazole metabolites would not contribute to the propiconazole-induced cytotoxicity process in primary mouse hepatocytes. Furthermore, since in tumor cell lines the metabolites were less cytotoxic than the parent propiconazole, our results suggest that in the tumorigenesis process as tumor cells are formed they would be more susceptible to the cytotoxic effects of propiconazole compared to the metabolites.
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PMID:Cytotoxic effects of propiconazole and its metabolites in mouse and human hepatoma cells and primary mouse hepatocytes. 1858 2

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 Sonic hedgehog (SHh) pathway plays a critical role in normal embryogenesis and carcinogenesis, but its function in cancer cells treated with 5-fluorouracil (5-FU) remains unknown. We examined the expression of a subset of SHh signaling pathway genes, including SHh, SMO, PTC1, Su(Fu) and HIP in human hepatocellular carcinoma (HCC) cell lines, Hep3B and HepG2, treated with 5-FU by reverse transcription-polymerase chain reaction. Using trypan blue analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling assay, we also detected the apoptosis of Hep3B cells resulting from the transfection of pCS2-Gli1 expression vector combined with 5-FU treatment. The motility of the cells was detected by scratch wound closure assay. The expression and subcellular location of PTC1 protein in Hep3B cells treated by 5-FU were also investigated by Western blot analysis and immunofluorescent microscopy. The results indicated that the expression of SHh pathway target molecules at both messenger RNA and protein levels are evidently down-regulated in Hep3B cells treated with 5-FU. The overexpression of Gli1 restores cell viability and, to some extent, the migration abilities inhibited by 5-FU. Furthermore, 5-FU treatment affects the subcellular localization of PTC1 protein, a key member in SHh signaling pathway. Our data showed that the down-regulation of SHh signaling pathway activity was involved in 5-FU-induced apoptosis and the inhibition of motility in hedgehog-activated HCC cell lines. This implies that the combination of SHh signaling pathway inhibitor and 5-FU-based chemotherapy might represent a more promising strategy against HCC.
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PMID:Down-regulation of Sonic hedgehog signaling pathway activity is involved in 5-fluorouracil-induced apoptosis and motility inhibition in Hep3B cells. 1877 95

Inonotus obliquus, a wild wood-decay fungus which grows on Betula trees in cool climates, has a variety of biological activities that the scientific community is paying more and more attention to. However, the research work is moving at a snail's pace. The methods of strain identification and the hypha microstructure have not been reported. We isolated one strain of filamentous molds from fruit body which was collected from birch wood on Changbai Mountain, cultivated mycelia on an inclined plane, and examined its micromorphology based on macroscopic examination. The strain was identified as I. obliquus by sequencing its ITS (internal transcribed spacer) domain. We subsequently investigated some of the mycelium polysaccharides' biological activities. The strain used in this study as the producers of antioxidation and anticancer polysaccharides was LNUF008. After fermentation in a 30-L fermenter, mycelia were obtained. The polysaccharides were extracted by transonic recirculation and ethanol precipitation. In order to identify the antioxidation effect, we designed an assay to test the inhibition of endogenous and Fe(2+)-Cys-induced lipid peroxidation as well as ferrous sulfate/ascorbate (Fe(2+)-VC)-induced mitochondrial swelling. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method was used to study the antiproliferation activity of the polysaccharides on SMMC7721 hepatoma cells. The results indicate that I. obliquus polysaccharides exhibit high antitumor and antioxidation effects. The submerged culture method of growing I. obliquus will enable large-scale production of the polysaccharides.
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PMID:Identification of Inonotus obliquus and analysis of antioxidation and antitumor activities of polysaccharides. 1879 65

Abnormal Savda Munziq (ASMq) is a traditional Uighur medicinal herbal preparation, commonly used for the treatment and prevention of cancer. We tested the effects of ethanol extract of ASMq on cultured human hepatoma cells (HepG2) to explore the mechanism of its putative anticancer properties, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide, neutral red and lactate dehydrogenase (LDH) leakage assays, testing the incorporation of (3)[H]-leucine and (3)[H]-nucleosides into protein, DNA and RNA, and quantifying the formation of malondialdehyde-thiobarbituric acid (MDA) adducts. ASMq ethanol extract significantly inhibited the growth of HepG2 and cell viability, increased the leakage of LDH after 48 hours or 72 hours treatment, in a concentration- and time-dependent manner (P < .05). Cellular protein, DNA and RNA synthesis were inhibited in a concentration- and time-dependent manner (P < .05). No significant MDA release in culture medium and no lipid peroxidation in cells were observed. The results suggest that the cytotoxic effects of ASMq ethanol extract might be related to inhibition of cancer cell growth, alteration of cell membrane integrity and inhibition of cellular protein, DNA and RNA synthesis.
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PMID:Inhibition of Cell Growth and Cellular Protein, DNA and RNA Synthesis in Human Hepatoma (HepG2) Cells by Ethanol Extract of Abnormal Savda Munziq of Traditional Uighur Medicine. 1895 70

The aim of this study is to assess whether fucoidan modulates the expression of chemokine ligand 12 (CXCL12)/chemokine receptor 4 (CXCR4) and exerts antitumor activity toward Huh7 hepatoma cells. According to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, fucoidan inhibited the growth of Huh7 cells and HepG2 cells in a dose-dependent manner, with a 50% inhibition of cell growth (IC50) of 2.0 and 4.0 mg/ml, respectively. alpha-fetoprotein levels in medium collected from fucoidan-treated cells were significantly decreased in Huh7 cells but not in HepG2 cells. Western blotting revealed that the amount of alpha-fetoprotein was decreased by 1.0 mg/ml of fucoidan in Huh7 cells, whereas it was unchanged in HepG2 cells. In Huh7 cells, CXCL12 mRNA expression was significantly downregulated by 1.0 mg/ml of fucoidan, whereas CXCR4 mRNA expression was unchanged by fucoidan. CXCL12 and CXCR4 mRNA were barely expressed in HepG2 cells. In addition, 1.0 mg/ml of fucoidan mildly arrested the cell cycle and induced apoptosis in Huh7 cells. The findings suggest that fucoidan exhibits antitumor activity toward Huh7 cells through the downregulation of CXCL12 expression.
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PMID:Inhibitory effect of fucoidan on Huh7 hepatoma cells through downregulation of CXCL12. 1937 7


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