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)

Hydroxycamptothecin (HCPT) is an antitumor alkaloid isolated from Camptotheca acuminata indigenous to China. It could reduce the activity of nuclear RNA polymerase II and I(III) of hepatoma cells. HCPT at 25-100 microM caused a remarkable inhibition on DNA polymerase alpha whilst only a slight inhibition on beta. The inhibitory action on alpha was restored by increasing amounts of enzyme or DNA template, but unchanged by varying amounts of substrate. It is suggested that HCPT may exert a stronger inhibition on DNA replication process.
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PMID:The effect of hydroxycamptothecin in the activity of RNA and DNA polymerases prepared from murine hepatoma cells. 402 12

(S)-10-Hydroxycamptothecin (OPT), an analog of camptothecin (CPT), was found to inhibit the growth of the mouse hepatoma BW7756, when given at 1.0 mg/kg/day for 14 days. Cell cycle studies using flow cytofluorometry indicated that this drug inhibited the S-Phase of the tumor cells in vivo and the S and G2/M phases in vitro. Similar studies on host liver showed little or no effect. In spite of the narrow range of the effective dose of this drug against mouse hepatoma BW7756, the use of OPT in combination with other antitumor agents may be useful in primary hepatoma or liver metastases in view of its low toxicity towards host liver. A simple cytofluorometric method useful for live cell cycle study has been adapted for this investigation and can be adopted for other drug studies.
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PMID:Anti-tumor effect of (S)-10-hydroxycamptothecin on mouse hepatoma BW7756 and its possible mode of action. 734 54

Hydroxycamptothecin (HCPT), isolated from Camptotheca acuminata, is a powerful antitumor alkaloid. Previous studies indicated that the molecular target of this agent was DNA topoisomerase I. The present results demonstrated that in vitro treatment of murine ascites hepatoma cells with HCPT resulted in a marked reduction in DNA syntheses and the inhibition of phosphorylation in histone was in a time-dependent manner. Gel electrophoresis found that HCPT had a selectively inhibitory effect on the phosphorylation of histone H1 and H3, but less effect on the other kinds of histones. In vivo, HCPT also exhibited a suppressive effect on histone H1 and H3 phosphorylation. These data suggested that HCPT-induced cell killing may be, at least in part, associated with the suppression of histone H1 and H3 phosphorylation.
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PMID:Inhibition of phosphorylation of histone H1 and H3 induced by 10-hydroxycamptothecin, DNA topoisomerase I inhibitor, in murine ascites hepatoma cells. 801 56

10-Hydroxycamptothecin (HCPT), a DNA topoisomerase I inhibitor, is an antitumor alkaloid isolated from a Chinese tree, Camptotheca acuminata, and exhibits a remarkable antihepatoma effect. We studied HCPT to determine whether or not its anti-hepatoma activity occurs through apoptosis induction and cell cycle disturbance using the MTT method, DAPI staining, agarose gel electrophoresis and flow cytometric analysis. The results showed that HCPT inhibited proliferation of human hepatoma Hep G2, Bel-7402 and Bel-7404 cells at an optimal concentration of 0.1 microg/ml. This growth inhibition was dose and time dependent, and was accompanied by evidence of apoptotic changes and cell cycle perturbation in Hep G2 cells. Chromatin condensation and nuclear fragmentation were observed in Hep G2 cells by fluorescence microscopy. Agarose gel electrophoresis showed internucleosomal DNA fragmentation ('ladder pattern') of Hep G2 cells following treatment with HCPT, in a concentration- and time-dependent manner. Flow cytometry showed that HCPT induced a massive hypodiploid cell population and arrested cells in G2/M phase (at low dose) or in S phase (at high dose) in Hep G2 cells. The results of this study suggest that the anti-hepatoma effect of HCPT may result from apoptosis induction and cell cycle disturbance.
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PMID:Apoptosis induction and cell cycle perturbation in human hepatoma hep G2 cells by 10-hydroxycamptothecin. 1088 5

10-Hydroxycamptothecin (HCPT), a DNA topoisomerase I (Topo I) inhibitor, exhibited a remarkable apoptosis-inducing effect on human hepatoma Hep G2 cells. We studied the effect of HCPT upon the expression of P53, c-Myc, Bcl-2, Bax and alpha-fetoprotein (AFP) proteins, and caspase (caspase-1 and caspase-3) activity of Hep G2 cells. It showed that HCPT at a dose of 0.1 microg/ml increased the expression of P53, c-Myc and Bax protein, and decreased the expression of Bcl-2 and AFP. The increase of P53, which was remarkable after only 3 h incubation with HCPT, occurred much earlier than the changes of other proteins, suggesting that the increase of P53 expression may be the upstream event in the apoptosis of Hep G2 cells induced by HCPT. Both caspase-1 and caspase-3 were activated in Hep G2 cells by HCPT treatment, suggesting that caspase-1 and caspase-3 are involved in the process of apoptosis in Hep G2 cells, and may be the main effectors of the apoptosis.
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PMID:Differential regulation of P53, c-Myc, Bcl-2, Bax and AFP protein expression, and caspase activity during 10-hydroxycamptothecin-induced apoptosis in Hep G2 cells. 1112 38

8,11-Dioxol-6-en-9alpha, 10alpha-epoxy-8beta-hydroxyeremophilane (HEM), a new eremophilanoid sesquiterpene, was isolated from Senecio oldhamianus Maxim. Its effects of cytotoxicity, telomerase activity, apoptosis and related genes expression in two human tumor cell lines, human hepatoma cells SMMC-7721 and human oophoroma cells HO-8910, were studied. Hydroxycamptothecine (HCPT) was used as a positive control. The IC50 of cytotoxicity by HEM were 24.9 +/- 2.1 and 19.4 1.6 microM in SMMC-7721 and HO-8910 cells respectively, and 0.35 +/- 0.10 and 0.27 +/- 0.08 microM for HCPT. HEM inhibited telomerase activity with the IC50 35.9 +/- 3.2 microM in SMMC-7721 and 25.6 +/- 2.6 microM in HO-8910 cells, while HCPT had no effect on telomerase activity in both tumor cell lines. HEM 20-30 microM induced apoptosis in SMMC-7721 cells from 5.7% to 18.4% and in HO-8910 cells from 7.6% to 67.1%. While HCPT 0.1-0.5 microM induced apoptosis in SMMC-7721 cells from 6.5% to 13.3% and in HO-8910 cells from 9.9% to 30.9%. HEM 30 microM significantly decreased Bcl-2 protein expression to 58.7% in SMMC-7721 and to 57.6% in HO-8910 cells. While HCPT 0.5 microM significantly decreased Bcl-2 protein expression to 64.3% in SMMC-7721 and to 70.0% in HO-8910 cells. HEM 25 microM and 30 microM significantly increased P53 protein expression 2.3-3.6-fold in SMMC-7721 and 3.0-5.7- fold in HO-8910 cells. While HCPT 0.5 microM significantly increased P53 protein expression 3.3-fold in SMMC-7721 and 2.7-fold in HO-8910 cells. Overall, HCPT exhibited a more potent effect on cytotoxicity and apoptosis in the two tumor cell lines than HEM did. However HEM can inhibit telomerase activity in the two tumor cell lines but HCPT cannot.
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PMID:In vitro effects on proliferation, telomerase activity and apoptosis of an eremophilanoid sesquiterpene from Senecio oldhamianus maxim in cultured human tumor cell lines. 1554 62

Hydroxycamptothecin-encapsulated chitosan (HC) nanospheres were prepared by Shirasu porous glass (SPG) membrane emulsification technique. The properties and morphology of HC nanospheres were characterized. The diameter of the nanospheres could be controlled within a narrow distribution according to the pore-size of SPG membrane. Hydroxycamptothecin (HCPT) encapsulation efficiency could reach to 81.3%. The long-term drug release of HCPT could be presented by an accumulated drug release of 85.4% in 15 days with an initial burst effect. In vitro study, HC showed its anti-tumor ability to human hepatoma (HepG2) cells. In vivo study, HC could reduce tumor weight and growth rate. The results indicated that HC nanospheres prepared by SPG had potential application as a sustained drug delivery system for the treatment of liver cancer.
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PMID:Synthesis and evaluation of hydroxycamptothecin-encapsulated chitosan nanospheres for the treatment of liver cancer. 2459 90

10-Hydroxycamptothecin (HCPT) is a clinical therapy agent against hepatoma. The chemotherapy of HCPT is strongly obstructed by the emergence of multidrug resistance (MDR), serious systemic toxicity, malfunction of rapid phagocytic and renal clearance disorder which are undesirable for its chemotherapy. In this paper, a drug delivery system (DDS) for HCPT has been developed in order to overcome MDR. Nanostructured lipid carriers (NLC) coated with xyloglucan (XG) was prepared by soya oil and XG consisting of side chains with galactose residues, a terminal moiety that can be used to target HCPT to hepatoma. The therapeutic potential of XG-NLC/HCPT was investigated on HepG2/HCPT cells and on human tumor xenograft nude mouse model (implanted with HepG2/HCPT cells). XG-NLC/HCPT not only indicated superior cytotoxicity against the drug resistant HepG2 cells but also in vivo, generated a higher therapeutic effect. Systemic toxicity study demonstrated that the carrier reduced systemic toxicity. XG-NLC/HCPT proved a great potential to serve as DDS to overcome MDR of HepG2/HCPT cells. These results suggested that XG NLC/HCPT represent a promising carrier for drug delivery to the hepatoma and reverse the drug resistant of HepG2 cells and XG could be exploited as a potential targeting device for liver tissue.
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PMID:Intracellular delivery of 10-hydroxycamptothecin with targeted nanostructured lipid carriers against multidrug resistance. 2642 82