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)

We examined the action of baicalein, a flavonoid contained in the herbal medicine sho-saiko-to (TJ-9), on three cell lines of human hepatocellular carcinoma (HCC). Treatment with baicalein strongly inhibited the activity of topoisomerase II and suppressed the proliferation of all three HCC cell lines. But the mode of cell death induced by baicalein differed according to the cell line. Baicalein induced apoptosis in a concentration-dependent manner in only one cell line, and an increased concentration of baicalein produced cell death via necrosis in the other two lines. These results suggest that the inhibition of topoisomerase II is not by itself sufficient for induction of apoptosis, and that there is a more important mechanism which can account for the difference in susceptibility of cells to apoptosis induced by baicalein.
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PMID:Cell death induced by baicalein in human hepatocellular carcinoma cell lines. 860 66

A 60-year-old male with hepatocellular carcinoma was treated by repeated intra-arterial injection of epirubicin, carboplatin and doxorubicin. Subsequently, radiotherapy and intravenous administration of etoposide were also carried out. Thirty-three months later he developed AML (M2). The chromosome analysis revealed 45, X, -Y, t (8;21) (q22;q22), which suggested that this leukemia was induced by topoisomerase II targeting agents. He was treated with low dose BHAC and G-CSF and achieved complete remission. This leukemia may be caused by synergic effect of topoisomerase II inhibitors and carboplatin together with radiotherapy. This may be the first report of therapy-related leukemia following chemotherapy for hepatocellular carcinoma.
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PMID:[Therapy-related AML(M2) with t(8;21) that developed three years after chemotherapy for hepatocellular carcinoma]. 869 93

Characteristics of multiple-drug resistance of rat ascites hepatoma AH66, a cell line induced by dimethylaminoazobenzene and established as a transplantable tumor, were compared with those of AH66F, a drug sensitive line obtained from AH66. The AH66 cell line was resistant to vinblastine, adriamycin, SN-38 an active form of camptothesine, etoposide, and clorambucil by 10-fold or more than the AH66F cell line. The resistance of AH66 cells to vinblastine, adriamycin, and SN-38 was closely related to P-glycoprotein overexpression in the plasma membrane, because the resistance was significantly inhibited by verapamil. AH66 cells contained much glutahione and had a high activity of glutathione S-transferase P-form (GST-P), compared with AH66F cells, and resistance to clorambucil was decreased by treatment with buthionine sulfoximine, an inhibitor of glutathione synthesis. AH66 cells have a similar topoisomerase I activity, but about 6 times lower topoisomerase II activity than AH66F cells. Therefore, the resistance to etoposide and a part of the resistance to adriamycin of AH66 cells seems to depend upon this low topoisomerase II activity. These results, show that the AH66 cell line has high multiple-drug resistance compared with the AH66F cell line, by several mechanisms. Consequently, the AH66 and AH66F cell lines are useful to study naturally acquired multiple-drug resistance of hepatomas.
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PMID:Characterization of naturally acquired multiple-drug resistance of Yoshida rat ascites hepatoma AH66 cell line. 870 43

DDB is a hepatoprotectant and has been widely used for the treatment of chronic viral hepatitis in China. The drug markedly improved the abnormal liver function particularly in lowering the elevated serum transaminases in patients. It is known that there is a close correlation between primary hepatocarcinoma and chronic viral hepatitis. The aim of the present study is to evaluate the effect of DDB on hepatocarcinoma cell line. The results showed that the growth and clonogenicity of Bel-7402 human hepatocarcinoma cell line cultured with DDB were markedly inhibited. The nucleoles of the cells treated with DDB disappeared or their numbers and nucleus/cytoplasm ratio decreased under electron microscopic observation. DDB at the concentration of 10(-4) mol.L-1 significantly increased the contents of cAMP and calmodulin (CaM) in Bel-7402 hepatocarcinoma cells. DDB was also found to inhibit topoisomerase II activity of Bel-7402 hepatocarcinoma cells. These results suggest that the mechanism of inhibition of DDB on several phenotypes of Bel-7402 cell line may be related to its effect on cAMP and CaM content as well as topoisomerase II activity.
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PMID:[Effect of dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2, 2'-dicarboxylate (DDB) on several phenotypes of Bel-7402 hepatocarcinoma cell line and its mechanism]. 876 69

Parathyroid hormone (PTH) alters osteoblast morphology. How these changes in cell shape modify nuclear structure and ultimately gene expression is not known. Chronic exposure to rat PTH (1-34) [10 nM] attenuated the expression of 200, 190, and 160 kD proteins in the nuclear matrix-intermediate filament subfraction of the rat osteosarcoma cells, ROS 17/2.8 [Bidwell et al. (1994b): Endocrinology 134:1738-1744]. Here, we determined that these same PTH-responsive proteins were expressed in rat metaphyseal osteoblasts. We identified the 200 kD protein as a non-muscle myosin. Although the molecular weights, subcellular distribution, and half-lives of the 190 and 160 kD proteins were similar to topoisomerase II-alpha and -beta, nuclear matrix enzymes that mediate DNA topology, the 190 and 160 kD proteins did not interact with topoisomerase antibodies. Nevertheless, the expression of topoisomerase II-alpha, and NuMA, a component of the nuclear core filaments, was also regulated by PTH in the osteosarcoma cells. The 190 kD protein was selectively expressed in bone cells as it was not observed in OK opossum kidney cells, H4 hepatoma cells, or NIH3T3 cells. PTH attenuated mRNA expression of the PTH receptor in our cell preparations. These results demonstrate that PTH selectively alters the expression of osteoblast membrane, cytoskeletal, and nucleoskeletal proteins. Topoisomerase II-alpha, NuMA, and the 190 and 160 kD proteins may direct the nuclear PTH signalling pathways to the target genes and play a structural role in osteoblast gene expression.
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PMID:Parathyroid hormone regulates the expression of rat osteoblast and osteosarcoma nuclear matrix proteins. 891 89

Progress in the treatment of hepatocellular carcinoma (HCC), a common tumor worldwide, has been disappointing. Inhibitors of topoisomerases are being widely studied as potential inducers of tumor cell apoptosis. Our aims were to determine whether topoisomerase-directed drugs would induce apoptosis in a human HCC cell line (Hep 3B) and, if so, to investigate the mechanism. The topoisomerase I poison camptothecin (CPT) induced apoptosis of Hep 3B cells in a time- and concentration-dependent manner. In contrast, the topoisomerase II poison etoposide failed to induce apoptosis despite the apparent stabilization of topoisomerase II-DNA complexes. Unexpectedly, CPT-induced apoptosis in this cell type occurred without any detectable cleavage of poly(ADP-ribose) polymerase or lamin B, polypeptides that are commonly cleaved in other cell types undergoing apoptosis. Likewise, Hep 3B cell apoptosis occurred without a detectable increase in interleukin-1beta-converting enzyme (ICE)-like or cysteine protease P32 (CPP32)-like protease activity. In contrast, trypsin-like protease activity (cleavage of Boc-Val-Leu-Lys-chloromethylaminocoumarin in situ) increased threefold in cells treated with CPT but not etoposide. Tosyl-lysyl chloromethyl ketone inhibited the trypsin-like protease activity and diminished CPT-induced apoptosis. These data demonstrate that (a) apoptosis is induced in Hep 3B cells after stabilization of topoisomerase I-DNA complexes but not after stabilization of topoisomerase II-DNA complexes as measured by alkaline filter elution; (b) Hep 3B cell apoptosis occurs without activation of ICE-like and CPP32-like protease activity; and (c) a trypsin-like protease activity appears to contribute to apoptosis in this cell type.
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PMID:Selective induction of apoptosis in Hep 3B cells by topoisomerase I inhibitors: evidence for a protease-dependent pathway that does not activate cysteine protease P32. 895 22

Scaffold or matrix attachment regions (S/MARs) are noncoding genomic DNA sequences displaying in vitro selective binding affinity for nuclear scaffold. They have been reported to be involved in the physical attachment of genomic DNA to the nuclear scaffold, and thus in the organization of the chromatin in functional loops or domains, and in the regulation of gene expression. In this work, we report the identification of an S/MAR in a woodchuck chromosomal locus, named b3n, previously described as a recurrent site of woodchuck hepatitis virus (WHV) DNA integration in woodchuck hepatocellular carcinoma (HCC). The 4.3-kb sequence of this locus contains several Alu-like repeats and a gag-like coding region with frameshift mutations. Computer analysis revealed the presence of a region with unusually high AT content, typical of most S/MARs, and of specific motifs (A boxes, T boxes, topoisomerase II sites, and unwinding elements) overlapping or in proximity to the region with high AT content, predicting that b3n might contain an S/MAR. Fragments of the b3n locus were isolated by conventional and inverse PCR techniques. In in vitro binding experiments with both heterologous and autologous scaffold preparations, a 592-bp fragment spanning the region rich in S/MAR features showed marked scaffold affinity, which was specific when autologous scaffolds were used. The presence of an S/MAR at the b3n locus and its nature as a recurrent WHV integration site in HCC suggest the involvement of S/MAR elements in some of the mechanisms leading to liver oncogenesis.
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PMID:Identification of scaffold/matrix attachment region in recurrent site of woodchuck hepatitis virus integration. 965 45

The nuclear enzyme topoisomerase II, which is involved in replication, transcription, and probably repair of DNA, can be inhibited by a number of flavonoids. In conjunction with X-rays, three of these compounds were tested as to their effects on Reuber H35 hepatoma cells. In this combination, the isoflavone genistein, the flavone apigenin, and the flavonol quercetin caused an enhancement of radiation-induced cell death. This enhanced cytotoxicity was only observed when the flavonoids were applied following an irradiation treatment and is attributed to decreased repair of DNA radiation damage with a concomitant reduction of the rate of cell repopulation. Fractionated irradiations, given as five sequences of 3 Gy each over a period of 5 days, reduced the surviving cell population only by a factor of 20, whereas the continuous presence of genistein during radiation sequences resulted in a reduction of at least a factor of 10,000. Thus, these flavonoids not only seem to act as radiation enhancers but also exhibit potential antitumor activities.
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PMID:Flavonoids as enhancers of x-ray-induced cell damage in hepatoma cells. 981 63

We investigated the expression of the drug resistance-related genes, multidrug resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), and the DNA topoisomerase IIalpha, DNA topoisomerase IIbeta, and glutathione-S-transferase pi gene (GST-pi) in three human hepatoma cell lines (HepG 2, HuH 7, SK-Hep-1) with or without drug treatment with interferon-alpha (IFN-alpha) and cisplatin (CDDP), by a reverse transcription-polymerase chain reaction (RT-PCR) method and a competitive PCR method. The signals of the MDR1, MRP, topoisomerase IIalpha, and topoisomerase IIbeta genes in HepG2 were weakened when IFN-alpha was added to CDDP. In SK-Hep-1, the administration of CDDP alone increased the signals of MDR1 while the addition of IFN-alpha decreased the signals, and the signals of GST-pi were decreased by IFN-alpha plus CDDP. In summary, our results concerning the expression of drug resistance-related genes in three human hepatoma cell lines demonstrate that IFN-alpha may modulate the mechanism of resistance to CDDP in liver cancer.
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PMID:Interferon-alpha modulates resistance to cisplatin in three human hepatoma cell lines. 1043 11

The objective of this study was to establish whether apoptosis in 5123tc rat hepatoma cells required the caspase-3 dependent pathway. Apoptosis was induced by either growth factor deprivation or treatment with a topoisomerase II inhibitor, VM26, in the absence or presence of caspase inhibitors (DEVD-fmk, z-VAD-fmk and BAF). The results indicated that, although these inhibitors at 10 microM concentration completely blocked caspase-3 activity, they had no effect on either the rate of cell death or on any other apoptotic features, e.g., chromatin condensation, DNA fragmentation, protein cleavage, suggesting that caspase-3 was not required to mediate nuclear destruction in these hepatoma cells. At higher concentrations, up to 100 microM, z-VAD-fmk and BAF, but not DEVD-fmk, did block apoptosis, however, they also caused cell swelling and membrane permeabilization, which are the hallmarks of necrotic cell death. Clearly, high concentrations of these inhibitors must have interfered non-specifically with other metabolic pathways, e.g., z-VAD-fmk at a high concentration blocked protein phosphorylation, and caused cell death by a different mechanism.
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PMID:Caspase-dependent and independent cell death in rat hepatoma 5123tc cells. 1122 48


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