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)

Our previous study showed that a methanol extract of Inula helenium had the potential to induce detoxifying enzymes such as quinone reductase (QR) and glutathione S-transferase (GST) activity. In this study the methanol extract was further fractionated using silica gel chromatography and vacuum liquid chromatography, to yield pure compounds alantolactone and isoalantolactone as QR inducers. Alantolactone caused a dose-dependent induction of antioxidant enzymes including QR, GST, gamma-glutamylcysteine synthase, glutathione reductase, and heme oxygenase 1 in hepa1c1c7 mouse hepatoma cells. The compound increased the luciferase activity of HepG2-C8 cells, transfectants carrying antioxidant response element (ARE)-luciferase gene, in a dose-dependent manner, suggesting ARE-mediated transcriptional activation of antioxidant enzymes. Alantolactone also stimulated the nuclear accumulation of Nrf2 that was inhibited by phosphatidylinositol 3-kinase (PI3K) inhibitors. In conclusion, alantolactone appears to induce detoxifying enzymes via activation of PI3K and JNK signaling pathways, leading to translocation of Nrf2, and subsequent interaction between Nrf2 and ARE in the encoding genes.
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PMID:Nrf2-mediated induction of detoxifying enzymes by alantolactone present in Inula helenium. 1870 92

This study was carried out to investigate the chemopreventive effects of immature plum extracts. The methanol extract of immature plums (plum 1), that are picked at 20-40 days before final harvest, has remarkably inhibited the growth of hepatoma HepG2 cells. The effects of immature plum extracts on hepatotoxicity in benzo(alpha)pyrene (B(alpha)P, carcinogen)-treated mice were investigated. Male ICR mice were pretreated with immature plum extracts (2.5 or 5 g/kg bw/day, for 5 days, i.p.) before treatment with B(alpha)P(0.5 mg/kg bw, i.p., single dose). The activities of serum aminotransferase, cytochrome P450 (CYPs) and the hepatic content of lipid peroxide were increased on B(alpha)P-treatment group than control, but those levels were significantly decreased by the pretreatment of immature plum extracts. The primary CYPs involved in the metabolism and bioactivation of B(alpha)P are CYP1A1. The pretreatment of immature plum extracts inhibited the induction of CYP1A1 expression. The activities of glutathione peroxidase, superoxide dismutase and catalase were decreased by the pretreatment of immature plum extracts more than with B(alpha)P alone. Whereas, the hepatic content of glutathione and glutathione S-transferase activity depleted by B(alpha)P was significantly increased (p > 0.05). These results suggest that immature plum extracts may counteract toxic effects of carcinogens, such as B(alpha)P, and therefore possess the chemopreventive efficacy.
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PMID:Inhibitory effects of methanol extract of plum (Prunus salicina L., cv. 'Soldam') fruits against benzo(alpha)pyrene-induced toxicity in mice. 1878 96

The antihepatoma activity and related active components in the fermentation products of Agaricus blazei (AB) cultured in the medium containing soybean (S) or black soybean (BS) were investigated. AB(BS)-pE and AB(S)-pE were the ethanolic extracts from the fermentation products of AB(BS) and AB(S), respectively. According to the IC 50 values, AB(BS)-pE (161.1 and 24.0 microg/mL for Hep 3B and Hep G2 cells, respectively) exhibited stronger cytotoxicities against hepatoma cells than AB(S)-pE (>200 and 99.9 microg/mL for Hep 3B and Hep G2 cells, respectively). AB(BS)-pE was separated by silica gel column chromatography and eluted with n-hexane/ethyl acetate/methanol gradient solvent system into 21 fractions. Fraction 3 [AB(BS)-pE-F3], eluted with n-hexane/ethyl acetate (97:3 and 19:1, v/v), was the most active fraction having inhibitory activity on the proliferation of Hep 3B and Hep G2 cells (IC 50 of 3.6 and 1.9 microg/mL, respectively). Three major compounds, compounds 1- 3, were further isolated from the AB(BS)-pE-F3 fraction by reversed-phase semipreparative high-performance liquid chromatography. Compounds 2 and 3 gave better antihepatoma activity than that of compound 1. The IC 50 values of compounds 2 and 3 were 2.8 and 4.5 microg/mL for Hep 3B cells and 1.4 and 2.0 microg/mL for Hep G2 cells, respectively. The structures of compounds 2 and 3 were identified by UV, IR, electron impact mass spectrometry, and (1)H and (13)C NMR to be blazeispirols A and C, respectively. Blazeispirols A and C existed in the mycelia but not in the broth and were more in AB(BS)-pE (49.9 +/- 8.9 and 14.2 +/- 2.4 mg/g, respectively) than AB(S)-pE (15.9 +/- 1.7 and 3.9 +/- 0.6 mg/g, respectively). Additionally, the result shows that the production of blazeispirols A and C was increased after cultivation in the medium containing black soybean on day 6 and reached the maximum on day 12, and the contents of blazeispirols A and C were negatively correlated with Hep 3B and Hep G2 cell viabilities ( r = -0.84 to -0.93, P < 0.01). It suggests that blazeispirols A and C could be used as biomarkers to produce the fermentation product of A. blazei with antihepatoma activity.
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PMID:Black soybean promotes the formation of active components with antihepatoma activity in the fermentation product of Agaricus blazei. 1880 46

In this study, we assessed the antitumor activity of the methanol extract from wood chips of the heartwood of the Taiwan red cypress, Chamaecyparis formosensis Matsumura, which is a precious tree species endemic to Taiwan. A brine shrimp lethality test (BST) indicated that the ethyl acetate (EtOAc)-soluble extract from the MeOH extract was a suitable candidate (LC (50) = 15.36 microg/mL) for further studies of the antitumor activity of its components. From this EtOAc fraction, we isolated six lignans and two norlignans and tested their cytotoxic activities IN VITRO against promyelocytic leukemia (HL-60) and hepatoma (Hepa-G2) cell lines. Among these compounds, 7,7'-( S)-dihydrotaiwanin C, isolated for the first time from nature, with its single crystal structure depicted in this study, exhibited significant cytotoxic activity against HL-60 cell lines IN VITRO (IC (50) = 4.03 microg/mL) after 24 hours. BST:brine shrimp lethality test Hepa-G2:human hepatoma HL-60:human leukemia IC (50):half-maximal inhibitory concentration SARs:structure-activity relationships AS:adenine sulfate.
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PMID:Isolation and cytotoxicity of the lignanoids from Chamaecyparis formosensis. 1900 28

We present herein the novel technique for constructing inverted cell-adhesion patternes on PEG gel modified glass surfaces by photoirradiation using the same photomask and materials. The PEG gel micropatterns were prepared by a photolithographic technique using a photomask with 100 microm aligned cavities after spin-coating of a mixed solution of alpha,omega-dimethacryloyl-PEG (PEG-DMA) and a photoinitiator on glass surfaces. When methanol was used as a casting solvent for the spin-coating (Method A), the circular PEG gel domains with a diameter of 100 microm were fabricated on the surface, and as would be predicted, seeded bovine aortic endothelial cells (BAECs) adhered to the glass area on the constructed surface to form a BAECs sheet with 100 microm aligned cavity. In contrast, it was rather surprising for us that a complete inverted cell pattern was formed when the PEG gel pattern surface was prepared using methanol/water co-solvent (Method B). Furthermore, when hepatoma cancer cells were seeded on the constructed surface prepared by Method B, they formed a spherical multicellular aggregate (spheroid) on the unmodified PEG gel domains without feeder cells. In order to obtain information on this peculiar phenomenon, fluorescence-based protein adsorption experiments, contact angle measurements, and X-ray photospectroscopy (XPS) analysis were carried out.
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PMID:Inverted pattern formation of cell microarrays on poly(ethylene glycol) (PEG) gel patterned surface and construction of hepatocyte spheroids on unmodified PEG gel microdomains. 1937 Feb 50

In the present study, we successively extracted the pu-erh raw tea with methanol (PR-1), chloroform (PR-2), ethyl acetate (PR-3), n-butanol (PR-4), and water (PR-5). Among these extracts, PR-3 extract contained ingredients with the most effective hypolipidemic potential and was further purified by column chromatography. Moreover, chronic administration of PR-3 provoked a significant reduction in levels of serum triglyceride and low-density lipoprotein (LDL) in rats. Our study demonstrated that fraction 5 from the PR-3 extract (PR-3-5s) showed a hypolipidemic effect in human hepatoma HepG2 cells. PR-3-5s decreased the expression of fatty acid synthase (FASN) and inhibited the activity of acetyl-coenzyme A carboxylase (ACC) by stimulating AMP-activated protein kinase (AMPK) through the LKB1 pathway. Moreover, PR-3-5s blocked the progression of the cell cycle at the G1 phase by inducing p53 expression and in turn upregulating p21 expression.
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PMID:Pu-erh tea attenuates hyperlipogenesis and induces hepatoma cells growth arrest through activating AMP-activated protein kinase (AMPK) in human HepG2 cells. 1945 11

Three known (1-3) and a novel (4) monoterpene indole alkaloids have been isolated from the methanol extract of leaves of Tabernaemontana elegans and their structures were elucidated by a series of spectroscopic experiments, involving NMR, MS, UV, and IR techniques. The isolated monoterpene indole alkaloids along with previously described beta-carbolines (5-7) from the same specimen were studied for their apoptosis induction activity in human hepatoma HuH-7 cells. Methodology for apoptosis induction studies included cell viability assays, nuclear morphology assessments, and general caspase-3-like activity assays. The monoterpene indole alkaloids, tabernaemontanine (1) and vobasine (3) showed the most promising apoptosis induction profile in HuH-7 cells.
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PMID:Induction of apoptosis in HuH-7 cancer cells by monoterpene and beta-carboline indole alkaloids isolated from the leaves of Tabernaemontana elegans. 1952 11

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. While searching for new natural anti-HCV agents in agricultural products, we found a potent inhibitor of HCV RNA expression in extracts of blueberry leaves when examined in an HCV subgenomic replicon cell culture system. This activity was observed in a methanol extract fraction of blueberry leaves and was purified by repeated fractionations in reversed-phase high-performance liquid chromatography. The final purified fraction showed a 63-fold increase in specific activity compared with the initial methanol extracts and was composed only of carbon, hydrogen, and oxygen. Liquid chromatography/mass-ion trap-time of flight analysis and butanol-HCl hydrolysis analysis of the purified fraction revealed that the blueberry leaf-derived inhibitor was proanthocyanidin. Furthermore, structural analysis using acid thiolysis indicated that the mean degree of polymerization of the purified proanthocyanidin was 7.7, consisting predominantly of epicatechin. Proanthocyanidin with a polymerization degree of 8 to 9 showed the greatest potency at inhibiting the expression of subgenomic HCV RNA. Purified proanthocyanidin showed dose-dependent inhibition of expression of the neomycin-resistant gene and the NS-3 protein gene in the HCV subgenome in replicon cells. While characterizing the mechanism by which proanthocyanidin inhibited HCV subgenome expression, we found that heterogeneous nuclear ribonucleoprotein A2/B1 showed affinity to blueberry leaf-derived proanthocyanidin and was indispensable for HCV subgenome expression in replicon cells. These data suggest that proanthocyanidin isolated from blueberry leaves may have potential usefulness as an anti-HCV compound by inhibiting viral replication.
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PMID:Proanthocyanidin from blueberry leaves suppresses expression of subgenomic hepatitis C virus RNA. 1953 80

Hypsizigus marmoreus has recently become a popular edible mushroom in Asia. Despite its extensive use, the underlying mechanisms of the anticarcinogenic effects on the initiation stage are not precisely known. Therefore, methanol extracts from H. marmoreus were prepared and then tested for antiproliferative effects in cancer cells and antimutagenic activities as well as mutagenic capacity using the Ames Salmonella mutagenicity test. In addition, the effects on the phase I drug metabolizing enzymes, phase II detoxifying enzymes, and antioxidative activities were evaluated in livers from mice pretreated with methanol extracts from H. marmoreus and challenged with benzo[a]pyrene (B[a]P). In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, methanol extracts from H. marmoreus displayed a dose-dependent inhibitory effect against human hepatocarcinoma and colon carcinoma cells. However, equivalent doses did not induce mutagenicity when tested with Salmonella typhimurium TA98 and TA100 while exhibiting antimutagenicity against direct-acting and indirect-acting mutagens. Methanol extracts from H. marmoreus strongly decreased total cytochrome P450 and activity of ethoxyresorufin deethylase after B[a]P challenge. Further investigation revealed that methanol extracts from H. marmoreus decreased protein levels of cytochrome P450 IAI isozyme induced by B[a]P. Methanol extracts from H. marmoreus increased the content of glutathione and activity of glutathione S-transferase. This also induced the activity of quinone reductase, an enzyme well known to be anticarcinogenic. The results of the present study therefore demonstrated that methanol extracts from H. marmoreus may have antimutagenic effects, inhibiting the mutagenicity of some mutagens, particularly indirect-acting B[a]P. The mechanism of this antimutagenicity may be the induction of the activity of phase II enzymes, as well as the ability to reduce phase I metabolic-activating enzymes in mouse liver.
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PMID:Cancer preventive potential of methanol extracts of Hypsizigus marmoreus. 1962 96

Warfarin is a well-known anticoagulant agent that occurs in two enantiomers, (R)-(+)-warfarin and (S)-(-)-warfarin. A new liquid chromatography method for the determination of both enantiomers was developed, validated and applied in in vitro studies with the aim of evaluating the accumulation of (R)-warfarin and (S)-warfarin in the hepatoma HepG2 cell line. OptiMEM cell cultivation medium samples and cellular lysates were purified using Waters Oasis MAX extraction cartridges. The chiral separation of warfarin and the internal standard p-chlorowarfarin enantiomers was performed on an Astec Chirobiotic V2 column at a flow rate of 1.2mL/min. The mobile phase was composed of 31% acetonitrile, 5% of methanol and 64% of ammonium acetate buffer (10mmol/L, pH 4.1). The enantiomers were quantified using a fluorescence detector (lambda(excit)=320nm, lambda(emiss)=415nm). The limit of detection was found to be 0.121micromol/L of (S)-warfarin and 0.109micromol/L of (R)-warfarin. The range of applicability and linearity was estimated from 0.25 to 100micromol/L. The precision ranged from 1.3% to 12.2% of the relative standard deviation, and the accuracy reached acceptable values from 95.5% to 108.4%. The new bioanalytical method confirmed the same accumulation of (R)-warfarin and (S)-warfarin in the hepatoma HepG2 cell line.
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PMID:New high-performance liquid chromatography method for the determination of (R)-warfarin and (S)-warfarin using chiral separation on a glycopeptide-based stationary phase. 1964 83


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