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)

The performance of alamar blue and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) cell viability assays in a high through-put format were compared. A total of 117 drugs chosen for their wide range of therapeutic areas were screened at 10 microM using both assays in human hepatoma cell line HepG2. Except for terfenadine and astemizole, which performed consistently in both assays, the alamar blue assay was slightly more sensitive than the MTT assay for most compounds. The MTT assay was less sensitive detecting an effect for daunorubicin and trifluoperazine. Seven drugs, astemizole, daunorubicin, ellipticine, fluphenazine, terfenadine, thioridazine and trifluoperazine, had percent viability results of 55% or less in the alamar blue assay at the single point screen. These were re-tested in both assays for reconfirmation of cytotoxicity and determination of the EC50 values. Except for daunorubicin, the EC50 values were comparable in both assays. Based on these results and the Z'-factor assessment of assay quality, both assays provided useful information to identify in vitro cytotoxic drugs at early stages of drug candidate selection. However, careful interpretation of data is warranted due to the possibility of false positive or negative results caused by inducers and/or inhibitors of metabolic enzymes that are responsible for transformation of cell toxicity end points, as we demonstrated using dicumarol.
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PMID:Comparison of alamar blue and MTT assays for high through-put screening. 1525 Nov 89

Data from clinical trails have shown that the antitumoral effect of ONYX-015, an E1B 55kDa-deficient adenovirus, as monotherapy is insufficient. To enhance its efficiency, CNHK200-mE, another E1B 55kDa-deficient adenovirus armed with a mouse endostatin gene was constructed and its antitumoral activities against hepatocellular carcinoma (HCC) in vitro and in vivo were investigated. The selective replication and cytotoxicity of CNHK200-mE in Hep3B and HepGII cells independent of p53 status were confirmed via TCID50 and 3-(4,5dimetylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assays. Potent tumor growth suppression on SMMC-7721 xenografts in nude mice was observed and a synergistic effect of the carrier virus and the therapeutic gene was suggested. Moreover, in comparison with the nonreplicative adenovirus carrying the same therapeutic gene, amplified transgene expression of mouse endostatin in vitro and in vivo were confirmed by Western blotting and ELISA assay. The effective angiogenesis inhibition and replication of CNHK200-mE in nude mice xenografts were demonstrated by immunohistochemistry. In conclusion, the recombinant adenovirus CNHK200-mE is a replication-competent oncolytic virus mediating high expression of therapeutic gene. Because CNHK200-mE is capable of replicating in and lysing HCC cells selectively with effective tumor growth suppression and antiangiogenic activity on HCC xenografts in nude mice, it holds good potential for the treatment of HCC.
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PMID:Potent antitumor efficacy of an E1B 55kDa-deficient adenovirus carrying murine endostatin in hepatocellular carcinoma. 1538 17

The present study examined the effect of hepatoma-associated antigen HAb18G (homologous to CD147) expression on the NO/cGMP-regulated Ca2+ mobilization to induce matrix metalloproteinases (MMP) production and attenuate adhesion ability of mouse fibroblast NIH/3T3 cells. HAb18G/CD147 cDNA was transfected into fibroblast 3T3 cells to obtain a cell line stably expressing HAb18G/CD147, t3T3, as demonstrated by immunofluorescence staining and flow cytometry assays. 8-Bromo-cGMP inhibited the thapsigargin-induced Ca2+ entry in 3T3 cells, whereas an inhibitor of protein kinase G, KT5823 (1 microM), led to an increase in Ca2+ entry. Expression of HAb18G/CD147 in t3T3 cells decreased the inhibitory response to cGMP. A similar effect on the Ca2+ entry was observed in 3T3 cells in response to an NO donor, (+/-)-S-nitroso-N-acetylpenicillamine (SNAP). The inhibitory effect of SNAP on the thapsigargin-induced Ca2+ entry was also reduced in HAb18G/CD147-expressing t3T3 cells, indicating a role for HAb18G/CD 147 in NO/cGMP-regulated Ca2+ entry. Results of gelatin zymography assays showed that addition of extracellular Ca2+ induced MMP (MMP-2, MMP-9) release and activation in a dose-dependent manner, and expression of HAb18G/CD147 enhanced the secretion of MMP-2 and MMP-9 in 3T3 cells. 8-Bromo-cGMP and SNAP reduced the production of MMP in 3T3 cells but not in t3T3 with HAb18G/CD147 expression. RT-PCR experiments substantiated that the expression of MMP-2 and MMP-9 mRNA in HAb18G/CD 147-expressing t3T3 cell was significantly greater than that in 3T3 cells. Experiments investigating adhesion potentials demonstrated that HAb18G/CD147-expressing t3T3 cells pretreated with Ca2+ attached to Matrigel-coated culture plates significantly less efficiently than 3T3 cells. The proportion of attached cells could be increased by treatment with 8-bromo-cGMP and SNAP in 3T3 cells, but not in t3T3. These results suggest that HAb18G/CD147 attenuates adhesion potentials in fibroblasts by enhancing the secretion of MMP through NO/cGMP-sensitive capacitative Ca2+ entry.
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PMID:HAb18G/CD147 enhances the secretion of matrix metalloproteinases (MMP) via cGMP/NO-sensitive capacitative calcium entry (CCE) and accordingly attenuates adhesion ability of fibroblasts. 1572 16

The protective effect of panduratin A, isolated from Kaempferia pandurata ROXB. (Zingiberaceae), against tert-butylhydroperoxide (t-BHP)-induced cytotoxicity was investigated in a human hepatoma cell line, HepG2. The tetrazolium dye colorimetric test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay) was used to monitor cytotoxicity. Lipid peroxidation [malondialdehyde (MDA) formation] and intracellular glutathione level were estimated by fluorometric methods. Intracellular reactive oxygen species (ROS) formation was measured using a fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA). Panduratin A significantly reduced the cell growth inhibition caused by t-BHP. Furthermore, panduratin A ameliorated lipid peroxidation as demonstrated by a reduction in MDA formation, and attenuated glutathione (GSH) depletion in a dose-dependent manner. It was also found that panduratin A reduced intracellular ROS formation caused by t-BHP. These results strongly suggest that panduratin A has significant protective ability against oxidative damage caused by reactive intermediates.
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PMID:Protective effects of panduratin A against oxidative damage of tert-butylhydroperoxide in human HepG2 cells. 1593 Jul 50

Lycopene, the predominant carotenoid in tomatoes and tomato-based foods, is reported to protect against various cancers, especially prostate cancer. We investigated the effect of lycopene on DNA damage and cell growth inhibition in the Hep3B human hepatoma cell line. Lycopene was analyzed by HPLC, and cell proliferation was determined by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. A final lycopene concentration of 0.1-50 microM was added to cells plated in 96-well plates. After a 24-hr incubation, cell viability was measured as absorbance at 570 nm after the MTT assay. The effects of lycopene on cell cycle progression were investigated with flow cytometry. Lycopene induced G0/G1 arrest and S phase block. Oxidative DNA damage was determined by the Comet (single-cell gel electrophoresis) assay. Lycopene inhibited cell growth in a dose-dependent manner. Cell growth was inhibited 20% at 0.2 microM lycopene and 40% at 50 microM lycopene after a 24-hr incubation. In the Comet assay, lycopene-treated cells showed less DNA damage than did placebo-treated cells. The inhibition of Hep3B cell growth in this study demonstrates the antitumor properties of lycopene.
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PMID:The effect of lycopene on cell growth and oxidative DNA damage of Hep3B human hepatoma cells. 1641 Jun 35

In an attempt to dissect the mechanism of Strychnos nux-vomica, a commonly used Chinese folk medicine in the therapy of liver cancer, the cytotoxic effects of four alkaloids in Strychnos nux-vomica, brucine, brucine N-oxide, strychnine, and isostrychnine, on human hepatoma cells (HepG2) were screened by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrasolium bromide (MTT) assay. Brucine, among the four alkaloids, exhibited the strongest toxic effect, the mechanism of which was found to cause HepG2 cell apoptosis, since brucine caused HepG2 cell shrinkage, the formation of apoptotic bodies, DNA fragmentation, cell cycle arrest, as well as phosphatidylserine externalization, all of which are typical characteristics of apoptotic programmed cell death. Brucine-induced HepG2 cell apoptosis was caspase dependent, with caspase-3 activated by caspase-9. Brucine also caused the proteolytic processing of caspase-9. In addition, brucine caused depolarization of the mitochondrial membrane of HepG2 cells, the inhibition of which by cyclosporine A completely abrogated the activation of casapses and release of cytochrome c in brucine-treated HepG2 cells. These findings suggested a pivotal role of mitochondrial membrane depolarization in HepG2 cell apoptosis elicited by brucine. Furthermore, brucine induced a rapid and sustained elevation of intracellular [Ca2+], which compromised the mitochondrial membrane potential and triggered the process of HepG2 cell apoptosis. Finally, Bcl-2 was found to predominately control the whole event of cell apoptosis induced by brucine. The elevation of [Ca2+]i caused by brucine was also suppressed by overexpression of Bcl-2 protein in HepG2 cells. From the facts given above, Ca2+ and Bcl-2 mediated mitochondrial pathway were found to be involved in brucine-induced HepG2 cell apoptosis.
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PMID:The apoptotic effect of brucine from the seed of Strychnos nux-vomica on human hepatoma cells is mediated via Bcl-2 and Ca2+ involved mitochondrial pathway. 1644 26

Hepatic progenitor cells (called oval cells in rodents) proliferate during chronic liver injury. They have been suggested as targets of malignant transformation in chronic liver diseases, including chronic hepatitis C. Interferon alpha therapy reduces the risk of hepatocellular carcinoma (HCC) in chronic hepatitis C regardless of viral clearance. The aim of this study was to determine whether interferon alpha could reduce the risk of HCC by modifying preneoplastic events in the hepatic progenitor cell population. Pre- and post-treatment liver biopsies were evaluated for changes in t he hepaticprogenitor cell population in 16 patients with non-responding chronic hepatitis C Interferon alpha-based treatment significantly reduced the numbers of c-kit-positive hepatic progenitor cells by 50%. To determine the mechanism of cell number reduction, the effects of interferon alpha on murinehepatic progenitor cells were studied in vitro. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay and proliferating cell nuclear antigen staining showed that interferon alpha had a dose-dependent, anti-proliferative effect Interferon alpha stimulated hepatocytic and biliary differentiation of the oval cell lines reflected by increased expression of albumin and cytokeratin19 accompanied by decreased expression of alphafetoprotein and Thy-1. To validatethese results in vivo, mice were placed on the choline-deficient, ethionine-supplemented diet to induce liver injury and oval cell proliferation and treated with pegylated interferon alpha 2b for 2 weeks. This resulted in a significant four-fold reduction in the number of oval cells (P < .05). In conclusion, interferon alpha-based treatment reduced the number of hepatic progenitor cells in chronic liver injury by modulating apoptosis, proliferation, and differentiation. Supplementay material for this article can
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PMID:Antiproliferative effects of interferon alpha on hepatic progenitor cells in vitro and in vivo. 1662 47

Several studies have recently reported the efficacy of combination therapy of interferon (IFN) alpha and 5-fluorouracil (5-FU) for hepatocellular carcinoma (HCC). However, the clinical effect of this treatment was not complete. The new therapeutic modality should be necessary to rise up this clinical response rate. Recently, the anti-tumor effect of Vitamin K2 has been reported in terms of decreased recurrence rate of HCC patients. The aim of this study was to explore the additive or synergistic effect of Vitamin K2 to combined therapy of interferon (IFN) alpha and 5-fluorouracil (5-FU) against hepatocellular carcinoma (HCCs). The study was conducted using three hepatoma cell lines (PLC/PRF/5, Hep3B and HepG2). The 3-(4-5-dimethylthiazol-2-yl)-2, 5-dyphenyl tetrazolium bromide (MTT) assay (48h) revealed anti-tumor effect of IFNalpha and 5-FU. Cell growth assay (3-7 days) showed growth inhibitory effect of Vitamin K2 on three cell lines after day 5. But additional effect of combination treatment of Vitamin K2 and IFNalpha/5-FU was not observed in any time course from 48h to 7 days. Cell cycles were assessed with flowcytometry. Although either Vitamin K2 or IFNalpha/5-FU alone has the influence to the cell cycles, no significant change was shown in the combination of Vitamin K2 and IFNalpha/5-FU. In conclusion, Vitamin K2 itself has potentially growth inhibitory effect for HCC cell lines, but does not enhance the anti-tumor effect of IFNalpha and 5-FU.
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PMID:Vitamin K2 has growth inhibition effect against hepatocellular carcinoma cell lines but does not enhance anti-tumor effect of combination treatment of interferon-alpha and fluorouracil in vitro. 1676 46

The growth inhibitory effects of D-glucosamine hydrochloride (GlcNH(2).HCl), D-glucosamine (GlcNH(2)) and N-acetyl glucosamine (NAG) on human hepatoma SMMC-7721 cells in vitro were investigated. The results showed that GlcNH(2).HCl and GlcNH(2) resulted in a concentration-dependent reduction in hepatoma cell growth as measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. This effect was accompanied by a marked increase in the proportion of S cells as analyzed by flow cytometry. In addition, human hepatoma SMMC-7721 cells treated with GlcNH(2).HCl resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis. NAG could not inhibit the proliferation of SMMC-7721 cells. GlcNH(2).HCl exhibited antitumor activity against Sarcoma 180 in Kunming mice at dosage of 125-500 mg/kg, dose of 250 mg/kg being the best. GlcNH(2).HCl at dose of 250 mg/kg could enhance significantly the thymus index, and spleen index and could promote T lymphocyte proliferation induced by ConA. The antitumor effect of GlcNH(2).HCl is probably host-mediated and cytocidal.
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PMID:Antitumor activities of D-glucosamine and its derivatives. 1684 12

N-(4-hydroxyphenyl)-retinamide (fenretinide) is a synthetic derivative of all-trans-retinoic acid and induces apoptosis in several cancer cell lines. We determined the anti-cancer activity of fenretinide using human hepatoma cell lines, Bel-7402, HepG2 and Smmc-7721. An in-vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that fenretinide exhibited growth inhibition in these cell lines, with IC50 values ranging from 13.1 to 15.5 micromol/l. In Bel-7402 cells, apoptosis with 15 micromol/l fenretinide for 0 and 48 h was 3 and 48%, respectively. In-vivo studies using the Bel-7402 xenografted athymic mouse model showed tumor inhibition rates ranging from 37.2 to 57.2%, with fenretinide administration once per 3 days at the rate of 25-100 mg/kg. Western blot analysis further showed down-regulation of procaspase-3, X-linked inhibitor of apoptosis protein and poly(ADP-ribose) polymerase cleavage in Bel-7402 cells treated with 15 mumol/l fenretinide for 48 h. Overexpression of p53 was observed in a time-dependent manner, along with a decrease in the Bcl-2/Bax ratio. Depolarized mitochondrial membranes were found in fenretinide-induced apoptotic cells, in a time-dependent manner. We conclude that fenretinide effectively inhibits the proliferation of Bel-7402, both in vitro and in vivo. Both procaspase-3 and p53-mediated apoptotic pathways are involved in its potent anti-cancer activity.
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PMID:Anti-proliferative activity of fenretinide in human hepatoma cells in vitro and in vivo. 1715 2


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