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)

Bitter gourd (Momordica charantia L.) is a common vegetable in Asia that has been used in traditional medicine for the treatment of Diabetes. PPARs are ligand-dependent transcription factors that belong to the steroid hormone nuclear receptor family and control lipid and glucose homeostasis in the body. We previously reported that the ethyl acetate (EA) extract of bitter gourd activated peroxisome proliferator receptors (PPARs) alpha and gamma. To identify the active compound that activated PPARalpha, wild bitter gourd EA extract was partitioned between n-hexane and 90% methanol/10% H(2)O, and the n-hexane soluble fraction was further separated by silica gel column chromatography and finally by preparative HPLC. A transactivation assay employing a clone of CHOK1 cells stably transfected with a (UAS)(4)-tk-alkaline phosphatase reporter and a chimeric receptor of GAL4-rPPARalpha LBD was used to track the active component. Based on Mass, NMR, and IR spectroscopy, 9cis, 11trans, 13trans-conjugated linolenic acid (9c, 11t, 13t-CLN) was identified as a PPARalpha activator in wild bitter gourd. The isolated 9c, 11t, 13t-CLN rich fraction also significantly induced acyl CoA oxidase (ACO) activity in a peroxisome proliferator-responsive murine hepatoma cell line, H4IIEC3, implying that 9c, 11t, 13t-CLN was able to act on a natural PPARalpha signaling pathway as well. The content of 9c, 11t, 13t-CLN was estimated to be about 7.1 g/kg of our dried wild bitter gourd sample. The concentration of 9c, 11t, 13t-CLN and activation activity in the hydrolyzed EA extract of the seeds was higher than that of the flesh. The potential health benefits of 9c, 11t, 13t-CLN through the PPARalpha regulated mechanism are worthy to be further characterized in in vivo studies.
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PMID:Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARalpha in bitter gourd (Momordica charantia L.). 1695 49

It was previously reported that a methanol extract of Gloiopeltis furcata (MEGF), a kind of edible seaweed, inhibited the growth of several human cancer cell lines. In the present study, the effect of MEGF on the growth of human hepatocarcinoma HepG2 cells and its effect on the cyclooxygenases (COXs) expression were investigated. MEGF markedly reduced the viability of HepG2 cells and induced the G2/M arrest of the cell cycle in a concentration dependent manner. These effects were associated with the down-regulation of cyclin A, up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) and dephosphorylation of Cdc25C. Furthermore, it was found that MEGF decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E(2) (PGE(2)) synthesis. These findings indicate that MEGF may have a possible therapeutic potential in hepatoma cancer patients.
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PMID:Methanol extract of the seaweed Gloiopeltis furcata induces G2/M arrest and inhibits cyclooxygenase-2 activity in human hepatocarcinoma HepG2 cells. 1707 9

Cadmium telluride (CdTe) nanoparticles exhibit strong and stable fluorescence that is attractive for many applications such as biological probing and solid state lighting. The evaluation of nanoparticle toxicity is important for realizing these practical applications. However, no systematic studies of CdTe nanoparticle toxicity have been reported. We investigated and compared the size- and concentration-dependent cytotoxicity of CdTe nanoparticles in human hepatoma HepG2 cells using the MTT assay. CdTe nanoparticles elicited cytotoxicity in a concentration- and size-dependent manner, with smaller-sized particles exhibiting somewhat higher potency. Lesser cytotoxicity of partially purified CdTe-Red particles (following methanol precipitation and resuspension) suggested that free cadmium ions may contribute to cytotoxicity. We also evaluated the acute toxicity of CdTe-Red particles following intravenous exposure in male rats (2 micromol/kg). Few signs of functional toxicity or clinical (urinary or blood) changes were noted. Interestingly, motor activity was transiently reduced (2 hours after treatment) and then significantly increased at a later timepoint (24 hours after dosing). These studies provide a framework for further characterizing the in vitro and in vivo toxic potential of different types of CdTe nanoparticles and suggest that the nervous system may be targeted by these nanoparticles under some conditions.
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PMID:In vitro and in vivo toxicity of CdTe nanoparticles. 1745 Jul 85

Temporin-1DRa (HFLGTLVNLAKKIL.NH(2)), first isolated from the skin of the California red-legged frog Rana draytonii, shows broad-spectrum antimicrobial activity but its therapeutic potential is limited by its toxicity against mammalian cells. The cytolytic properties of cationic alpha-helical peptides are determined by a complex interaction between cationicity, hydrophobicity, conformation, and amphipathicity. This study has investigated the cytolytic properties of conformationally constrained analogs of temporin-1DRa containing alpha-aminoisobutyric acid (Aib) substitutions. Cytolytic activity was determined against the bacteria Escherichia coli and Staphylococcus aureus, the opportunistic yeast pathogen, Candida albicans, human erythrocytes, HepG2 hepatoma-derived cells, and L929 fibroblasts. Aib substitutions at Gly(4), Asn(8), and Ala(10) increased both % helicity, determined in methanol solution, and hydrophobicity resulting in increases in both antimicrobial potencies and toxicities against the mammalian cells. Substitution at Leu(6) resulted in an appreciable decrease in cytolytic activity against all cells whereas the substitutions at His(1), Phe(2), Leu(3), Thr(5), and Val(7) had only minor effects on activity. Substitutions at Leu(9), Ile(13), Leu(14) produced analogs with decreased helicity and hydrophobicity that retained activity against microorganisms but showed appreciably lower cytolytic activities against mammalian cells. In particular, the fourfold increase in therapeutic index [ratio of LC(50) against erythrocytes to minimum inhibitory concentration (MIC) against microorganisms] of [Aib(13)]temporin-1DRa identifies it as a compound with potential for development as a therapeutically valuable anti-infective agent.
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PMID:Effect of aminoisobutyric acid (Aib) substitutions on the antimicrobial and cytolytic activities of the frog skin peptide, temporin-1DRa. 1776 78

The study of bioactivity of natural product is one of the major researches for drug discovery. The aim of this finding was to study the proliferation effect of Rhaphidophora korthalsii methanol extract on human PBMC and subsequently the cytotoxic effect of activated PBMC toward HepG2 human hepatocellular carcinoma. In this present study, MTT assay, cell cycle study and Annexin 5 binding assay were used to study the immunomodulatory and cytotoxic effects. In vitro cytotoxic screening of Rhaphidophora korthalsii methanol extract showed that the extract was non-toxic against hepatocellular carcinoma (HepG2). In contrast, the extract was able to stimulate the proliferation of human PBMC at 48 h and 72 h in MTT assay and cell cycle progress study. The application of immunomodulator in tumor research was studied by using MTT microcytotoxicity assay and flow cytometric Annexin V. Results indicated that pre-treated PBMC with Rhaphidophora korthalsii methanol extract induced the highest cytotoxicity (44.87+/-6.06% for MTT microcytotoxicity assay and 51.51+/-3.85% for Annexin V) toward HepG2. This finding demonstrates that Rhaphidophora korthalsii methanol extract are potent to stimulate the cytotoxic effect of immune cells toward HepG2.
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PMID:Effect of Rhaphidophora korthalsii methanol extract on human peripheral blood mononuclear cell (PBMC) proliferation and cytolytic activity toward HepG2. 1788 17

The subject of the study was the unidentified protein Ag A2/3, which is found in some cells of rat hepatoma McA RH7777 and their clones. The feature of this protein is that its expression is alternative to alfa-fetoprotein (AFP), i.e. Ag A2/3 is not found in cells and cell clones containing AFP, and vice versa. Ag A2/3 proved to be a cell stress protein--it was induced by heavy metal salts (Pb2+ and Cd2+) in the liver of adult rats and AFP+/A2/3(-) clones of hepatomas; the attenuation of AFP synthesis occurred simultaneously. This paper describes the preparation of Ag A2/3 for sequence analysis, and the scheme of Ag A2/3 purification. When trying to obtain a blot for sequencing it proved to be impossible to reveal the protein using McAb to Ag A2/3 after the transfer of separated proteins on PVDF. The reactivity of the antigen determinant was reestablished with blot processing on PVDF membrane with methanol and Twin 80.
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PMID:[The purification of the protein alternative to alfa-fetoprotein]. 1808 30

The present study developed a validate and precise reversed-phase high performance liquid chromatography (HPLC) method for the determination of thalidomide (T) in plasma, to quantify T in patients affected by hepatocellular carcinoma. Twelve male subjects aging from 62 to 82 years and weighting 66-88kg, were orally administered with single dose of T (200mg/BW). Two ml of stabilizer-solution (CH3OH/CH3CN, 1/1 (v/v)+CH3COOH 2%) were added to 1ml of human plasma and stoked to -80 degrees C until analyses. This moisture (1.38microl) was added with 20microl of CF3COOH and 100microl of phthalimide (IS) 1.75microg/ml, vortexed and centrifuged. Surnatant (800microl) was dried under vacuum at room temperature, added with 50microl of appropriate solution and injected onto HPLC. T and IS were detected at UV wavelength of 220nm with a run time of 10min. Mobile phase was 10mM pH 5.5NH4+CH3COO-/CH3CN, 75/25 (v/v) buffer at flow rate of 1.5ml/min. Inter-day and intra-day variation coefficient was <10% with an error of accuracy <10%. The present detection method was able to quantify T to every withdrawal time period (LOD 0.05microg/ml). The IS used in the present study had the same wavelength maximum absorption of T, differently from early UV detection methods reported in literature where phenacetin was used. Pharmacokinetic parameters belonging from the present study are not significantly different from those calculated in previously studies performed in human health subjects and patients affected by other pathology.
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PMID:High performance liquid chromatographic determination of thalidomide in patients affected by hepatocellular carcinoma. 1828 76

The herb of Oldenlandia diffusa (Willd.) Roxb. (Family Rubiaceae) is well-known in Chinese folk medicine for the treatment of hepatitis and malignant tumors of the liver, lung and stomach. However, another herb of O. corymbosa (L.) Lam is also used interchangeably in South China for treating the same conditions. To compare the efficacy of the two herbs, the antiproliferative effect of their extracts and the antiangiogenic activity of their main constituents were appraised. The Sulforhodamine B (SRB) assay in human hepatoma HepG2 cells and human colon carcinoma CaCo2 cells and the zebrafish angiogenic model were used for this purpose. The results showed almost no antiproliferative effect of the methanol extracts from O. diffusa and O. corymbosa, while the chloroform extracts exhibited slightly antiproliferative effects. The main components had almost no effect on zebrafish angiogenic vessel formation at the concentrations tested. The results suggest that the mechanism of antitumor activity of O. diffusa may not be attributed to the antiproliferative and antiangiogenic effects.
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PMID:A comparable, chemical and pharmacological analysis of the traditional Chinese medicinal herbs Oldenlandia diffusa and O. corymbosa and a new valuation of their biological potential. 1833 27

The growth inhibition and the induction of apoptosis brought about by soyasaponins extracted from soy flour ( Glycine max (L.)) and concentrated for soyasapogenols A and B formed by hydrolysis were tested for cytoactivity in the human hepatocellular carcinoma cell line Hep-G2. Concentrated soyasapogenol A (SG-A) and soyasapogenol B (SG-B) extracts contained approximately 69.3% and 46.2% of their respective aglycones (soyasapogenols) assessed by HPLC and ESI-MS, while the soyasaponin extract (TS), derived from crude methanol extraction, did not contain any detectable amounts of SG-A or SG-B. An MTT viability assay showed that all three extracts had an effect on Hep-G2 proliferation in a dose-response manner with 72 h LC50 values of 0.594+/-0.021 mg/mL for TS, 0.052+/-0.011 mg/mL for SG-A, and 0.128+/-0.005 mg/mL for SG-B. Apoptotic cells were determined by flow cytometry cell cycle analysis and confocal laser scanning microscopy (CLSM). Cell cycle analysis indicated a significant ( P< 0.05) greater sub-G1 buildup of apoptotic cells at 24 h (25.63+/-2.1%) and 72 h (47.1+/-3.5%) for the SG-A extract compared to SG-B, whereas the TS extract produced only a minor buildup of sub-G1 cells. CLSM confirmed a morphological change of all treatments after 24 h, at the respective LC50 concentrations. These results show that the samples that contained mainly soyasapogenols A and B showed a greater ability to inhibit proliferation of cultured Hep-G2 when compared to a total soyasaponin extract that did not contain any soyasapogenols.
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PMID:Effect of soyasapogenol A and soyasapogenol B concentrated extracts on HEP-G2 cell proliferation and apoptosis. 1836 99

Anisomeles indica (L.) Kuntze (Labiatae), is a traditional anti-inflammatory herb used in Taiwan. The aqueous and methanolic extracts of whole plants, leaves, flowers and stems; and chloroform and n-butanol fractions of methanol extract, from A. indica were investigated for their anti-inflammatory activity on murine peritoneal macrophages. In addition, the tumor cells proliferation inhibition activities of these extracts were also evaluated against a panel of tumor cell lines such as Colon 205, PC 3, HepG2 and MCF 7. Treatment with A. indica extracts did not reduce cell viability at any dose used. However, all the extracts significantly inhibited the enhanced production of NO radicals, and pro-inflammatory cytokines (TNF-alpha, and IL-12) induced by LPS/IFN-gamma in a dose-dependent manner. Furthermore, methanolic extracts of leaves and flowers significantly and dose-dependently arrest mitogen-stimulated spleen cells in G0/G1 stage, in addition to their cell proliferation inhibition against Colon 205, MCF 7 and PC 3 by 94, 82; 98, 71; 82, 98%, respectively, at 200 microg/mL concentration. This is the first report on A. indica extracts for their growth inhibitory activities, against inflammatory mediator production, and human tumor cell lines, colon, prostate, hepatoma and breast cells proliferation.
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PMID:Inhibition of pro-inflammatory mediators and tumor cell proliferation by Anisomeles indica extracts. 1844 Jan 71


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