• Journal of Ginseng Research
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• v.19 no.3
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• pp.212-218
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• 1995

A human hepatoma cell line, hep G2, was used to investigate the mechanism of serum cholesterol reduction by ginseng total saponin, ginsenoside-$Rb_1$, - $Rb_2$, and non-saponin fraction (ether extraction). Hep G2 cells were incubated in 10 $\mu\textrm{g}$/ml of cholesterol containing serum free-RPMl1640 medium with various concentration of ginseng components. The amounts of cholesterol in Hep G2 cells were decreased to maximum 51% in total saponin or two ginsenoside-treated groups while there was 137% increase in cholesterol level of control group as compared with that of normal group. Nonsaponin groups did not show the same effect. In order to elucidate the observed changes in the amount of cholesterol, the activity of amyl CoA : cholesterol acyltransferase (ACAT) in groups showing remarkable reduction in cholesterol amount, i.e., total saponin 10-6%, ginsenoside-$Rb_1$ $10^{-4}$%, ginsenoside-$Rb_2$, $10^{-4}$%, and non-saponin fraction $10^{-4}$%, was assayed using [1-$^{-14}C$%]oleic acid as enzyme substrate. The activity of ACAT was increased in all groups tested as compared with that of control group except for non-saponin group cultured in water soluble cholesterol containing medium. The serum cholesterol lowering effects of ginseng components can partially be attributed to the increased hepatocellular ACAT activity.

• Journal of Life Science
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• v.17 no.6 s.86
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• pp.766-771
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• 2007

The co-infection with hepatitis B virus (HBV) and hepatitis C Virus (HCV) is associated with a more severe liver disease and increased frequency in the development of hepatocellular carcinoma com-pared to those with single infection. Here, we demonstrated that HBV X protein (HBx) and HCV Core cooperatively up-regulated the level of p53 in human hepatoma HepG2 cells. The elevated p53 subsequently stimulated the expression of proapoptotic Bax whereas it repressed the expression of antiapoptotic Bcl2. These effects, however, were not observed in p53-negative Hep3B cells. Consistently to their cooperative regulation of apoptotic effectors, HBx and HCV Core additively stimulated cisplatin-mediated apoptotic cell death of HepG2 but not of Hep3B cells. These results may help to explain the development of a more severe liver disease in patients co-infection with HBV and HCV as well as some contradictory results on the roles of HBx and Core in apoptosis.

• Journal of Convergence Korean Medicine
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• v.5 no.1
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• pp.45-54
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• 2023

Objectives : Alcohol-induced liver disease advances as to reactive oxygen species (ROS) and cellular lipid peroxidation increase. We examined the hepatoprotective effects of Zingiber officinale Roscoe rhizome extract (ZR), Pueraria lobata Ohwi flower extracts (PF), and a newly developed herbal juice (HJ), which was a combination of ZR and PF extracts, against ethanol-induced hepatotoxicity. Methods: The study utilized the human hepatoma cell line HepG2 cells to validate the hepatoprotective effect of HJ (50~200 ㎍/mL) against ethanol (EtOH, 700 mM)-induced liver damage. Results: HJ effectively reduced the protein expression of sterol regulatory element-binding transcription factor 1, adiponectin, and AMP-activated protein kinase in EtOH-induced HepG2 cells. The levels of ROS, total cholesterol, and triglycerides, which are the result of various synthesis and lipogenesis processes induced by EtOH in the liver, were reduced by HJ. Furthermore, the activities of alcohol dehydrogenase and aldehyde dehydrogenase, enzymes linked to alcohol degradation, were more effectively downregulated by HJ treatment compared to treatment with ZR and PF alone, all without causing cytotoxic effects. Conclusions: HJ protects the liver by inhibiting EtOH-induced lipogenesis, lowering ROS generation, and improving alcohol degradation, which is more effective than ZR and PF alone. Further, in vivo experiments can offer additional evidence regarding the effectiveness, safety, and underlying mechanism of action of HJ.

• Analytical Science and Technology
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• v.18 no.2
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• pp.104-111
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• 2005

Several solvents were used to fractionate an extract obtained from the chapped root bark of Ulmus davidiana Planchon. The each fractionary part was condensed under reduced pressure and then examined to investigate the inhibitory effect on MMPs by modified gelatin zymography, where EA fraction showed the inhibition effect on the activity of MMPs. A compound showing inhibition effect on the MMPs was isolated and purified from EA fraction. Under IR, $^1H$- and $^{13}C$- NMR analyses it is very close to a catethin. This substance showed 48% inhibition effect on measurement of MMP-9 activity at 5 mM and 43% at 10 mM. To verify the effect of this substance on cells, human hepatoma, SK-Hep-1 cells as a cancer model, and Chang liver cells as a normal model were selected. MTT assay was performed to examine the cell viability by treatment of $1{\mu}L/mL$ of the purified substance on cells. The purified substance showed negligible toxicity on human liver cell line.

• Korean Journal of Food Science and Technology
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• v.36 no.4
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• pp.662-668
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• 2004

Ames test revealed most methanol extracts of 13 Korean wild mushroom species have strong antimutagenic effects against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and benzo(a)pyrene[B(a)P]. Methanol extracts of Coriolus versicolor and Phaeolepiota aurea showed 74-94 and 83-88% antimutagenic effects against MNNG and B(a)P in Salmonella typhimurium TA100 strain, while 89 and 91% inhibitions were observed against B(a)P in TA98 strain, respectively. Most water extracts of wild mushrooms did not show antimutagenic activeiy on MNNG and B(a)P. Wild mushrooms extracts inhibited human colon carcinoma cells (HT29), human hepatoma cell (HepG2), and humann histiocytic lymphoma cell (U937) dose-dependently, with most methanol extracts exhibiting stronger effect than water extracts, Highest toxicity was observed against HT-29 cells in methanol extracts of Coriolus versicolor and Phaeolepiota aurea, showing 84% inhibition at 1 mg/mL, whereas C. versicolor water extract showed 53-65% inhibition against HepG2 and U937. These extracts did not show cytotoxic effects against human lymphocyte. Results revealed wild mushrooms have strong antimutagenic and in vitro cytotoxic effects.

• Journal of Acupuncture Research
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• v.23 no.3
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• pp.177-190
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• 2006

Objectives : It has long been known about the anticancer effect of GRR-HAS, however, it has not been systemically determined the differentially regulated genes by GRR-HAS in cancer cells. The purpose of this study is to screen the GRR-HAS mediated differentially expressed genes in cancer cells such as HepG2 hepatoma cell lines. Oligonucleotide microarray and proteomic approaches were employed to screen the differential expression genes. Methods : GRR~HAS was prepared by boiling and stored at $-70^{\circ}C$ until use. Cells were treated with various concentrations of GRR-HAS (0.1, 0.5, 1.5, 10, $20mg/m{\ell}$) for 24 h. Cell toxicity was tested by MTT assay. To screen the differentially expressed genes in cancer cells, cells were treated with $1.5mg/m{\ell}$ of GRR-HAS. For oligonucleotide microarray assay, total RNA was used for gene expression analysis using oligonucleotide genechip (Human genome Ul33 Plus 2.0., Affimatrix Co.). For proteomic analysis, total protein was analyzed by 2D gel electrophoresis and Q-TOF mass spectrometer. Results : It has no cytotoxic effects on both HepG2 cells in all concentrations(0.1, 0.5, 1.5, 10,$20mg/m{\ell}$). In oligonucleotide microarray assay, the number of more than twofold differentially regulated known genes was 320 with 6 up-regulated and 314 down-regulated genes in HepG2 cells. In proteomic analysis, three spots were identified by 2D-gel electrophoresis and Q-TOF analysis. One down -regulated protein was protein disulfide isomerase and up-regulated proteins were fatty acid binding protein 1 and 14-3-3 gan1lTIa protein by $1.5mg/m{\ell}$ of CRR-HAS. Discussion : This study showed the comprehensive gene expression analysis using oligonucleotide microarray for the screening of GRR-HAS mediated differentially regulated genes. These results will provide a better application of GRR-HAS in cancer field and drug target development.

• Journal of Radiation Protection and Research
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• v.25 no.4
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• pp.183-190
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• 2000

Medicinal plants with synergistic effects on growth inhibition of canter cells under oxidative stress were screened in this study. Methanol extracts from 51 natural medicinal plants which were reported to have anticancer effort on hepatoma stomach cancer or colon cancers which are frequently found in Korean, were prepared and screened for their synergistic activity on growth inhibition of cancer cells under chemically-induced oxidative stress by using MTT assay. Twenty seven samples showed synergistic activity on the growth inhibition in various extent under chemically-induced oxidative stress. Among those samples, eleven samples such as Melia azedarach, Agastache rugosa, Catalpa ovata, Prunus persica, Sinomenium acutum Pulsatilla koreana, Oldenlandia diffusa, Anthriscus sylvestris, Schizandra chinensis, Gieditsia sinensis, Cridium officinale, showed decrease in $IC_{50}$ values more than 50%, other 16 samples showed decrease in $IC_{50}$ values between 50-25%, compared with the value acquired when medicinal plant sample was used alone. Among those 11 samples, extract of Catalpa ovata showed the highest activity. $IC_{50}$ values were decrease to 61% and 28% when carcinoma cells were treated with Catalpa ovata extract in combination of 75 and 100 uM of hydrogen peroxide, respectively.

• Journal of Life Science
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• v.19 no.12
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• pp.1731-1736
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• 2009

Recent studies determined that a chronic western-style diet increased the endogenous small heterodimer partner (SHP) protein levels in mice. In experiments with cell cultures, chenodeoxy cholic acid (CDCA) treatment increased endogenous SHP protein levels and reduced the degradation rate of exogenously expressed flag-SHP levels in the human hepatoma cell line, HepG2 cells. In addition, bile acid-induced intestinal fibroblast growth factor-19 (FGF-19) increased the half-life of the exogenously expressed SHP when HepG2 cells were transfected with ad-flag-SHP. However, both the expression level and the degradation rate of the endogenous SHP in response to cholic acid and FGF-19 have not been well understood, either in mice or in cultured HepG2 cells. This study examined the effects of cholic acid treatment on the endogenous SHP protein levels in mice and the effects of FGF-19 on the degradation rate of the endogenous SHP protein in HepG2 cells. Mice fed 0.5% cholic acid in normal chow showed an increase in endogenous SHP protein levels during both 12 hr and 24 hr treatment periods as compared to control mice fed only normal chow. In cultured HepG2 cells, treatment with CDCA did not noticeably change the rate of degradation in the endogenous SHP protein from cells not treated with CDCA. Although consistent with the previous studies on the exogenous ad-flag-SHP protein, treatment with FGF-19 significantly decreased the degradation rate of the endogenous SHP protein when HepG2 cells were treated with cyclohexamide. These results suggest that both bile acids and FGF-19 increase the endogenous SHP protein levels in mouse liver and HepG2 cells.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.859-865
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• 2006

With an approach to study the anti-tumor effects and mechanism of selenium compound, we investigated the anti-tumor activity and mechanism of $Na_5SeV_5O_{18}{\cdot}3H_2O$ (NaSeVO) in K562 cells. The results showed that $0.625{\sim}20\;mg/L$ NaSeVO could significantly inhibit the proliferation of K562 cells in vitro in a time- and concentration-dependent manner as determined by microculture tetrazolium (MTT) assay, the IC50 values were 14.41 (4.45-46.60) and 3.45 (2.29-5.22) mg/L after 48 hand 72 h treatment with NaSeVO respectively. In vivo experiments demonstrated that i.p. administration of 5, 10 mg/kg NaSeVO exhibited an significant inhibitory effect on the growth of transplantation tumor sarcoma 180 (S180) and hepatoma 22 (H22) in mice, with inhibition rate 26.8% and 58.4% on S180 and 31.3% and 47.4% on H22, respectively. Cell cycle studies indicated that the proportion of G0/G1 phase was increased at 2.5 mg/L while decreased at 10 mg/L after treatment for 24, 48 h. Whereas S phase was decreased at 2.5-5 mg/L and markedly increased at 10 mg/L after treatment for 48 h. After treatment for 24 h, 10 mg/L NaSeVO also markedly increased S and G2/M phases. Take together, the result clearly showed that NaSeVO markedly increased S and G2/M phases at 10 mg/L. The study of immunocytochemistry showed that the expression bcl-2 is significantly inhibited by 10 mg/L NaSeVO, and bax increased. Morphology observation also revealed typical apoptotic features. NaSeVO also significantly caused the accumulation of $Ca^{2+}$ and $Mg^{2+}$, reactive oxygen species (ROS) and the reduction of pH value and mitochondrial membrane potential in K562 cells as compared with control by confocal laser scanning microscope. These results suggest that NaSeVO has anti-tumor effects and its mechanism is attributed partially to apoptosis induced by the elevation of intracellular $Ca^{2+}$, $Mg^{2+}$ and ROS concentration, and a reduction of pH value and mitochondria membrane potential (MMP).

• Journal of Pharmacopuncture
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• v.9 no.2
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• pp.5-16
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• 2006

Objective : It has long been known about the osteogenic effect of CPC-HAS on bone tissues. However, it has not been determined the effect of CPC-HAS on cancer cells. The purpose of this study is to screen the CPC-HAS mediated differentially expressed genes in cancer cells such as HepG2 hepatoma cells. Oligonucleotide microarray and proteomics approaches were employed to screen the differential expression genes. Methods : CPC-HAS was prepared by boiling and stored at $-70^{\circ}C$ until use. Cells were treated with various concentrations of CPC-HAS (0.1, 0.5, 1.5, 10, 20mg/ml) for 24 h. Cell toxicity was tested by MTT assay. To screen the differentially expressed genes in cancer cells, cells were treated with 1.5mg/ml of CPC-HAS. For oligonucleotide microarray assay, total RNA was used for gene expression analysis using oligonucleotide Genechip(Human genome Ul33 Plus 2.0., Affimatrix Co.). For proteomic analysis, total protein was analyzed by 2D gel electrophoresis and Q-TOF mass spectrometer. Results : It has no cytotoxic effects on both HepG2 cell in all concentrations(0.l, 0.5, 1.5, 10, 20mg/ml). In oligonucleotide microarray assay, the number of more than twofold differentially regulated known genes was 23 with 5 up-regulated and 18 down-regulated genes in HepG2 cells. In proteomic analysis, three spots were identified by 2D-gel electrophoresis and Q-TOF analysis. Two down-regulated proteins were aldehyde dehydrogenase 1 and enolase 1, and up-regulated protein was fatty acid binding protein 1 by 1.5mg/ml of CPC-HAS. Discussion : This study showed the screening of CPC-HAS mediated differentially regulated genes using combined approaches of oligonucleotide microarray and proteomic analysis. The screened genes will be used for the better understanding of the therapeutic effects of CPC-HAS on cancer fields.