• Microbiology and Biotechnology Letters
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• v.49 no.4
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• pp.594-602
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• 2021

The NLRP3 (nucleotide-binding domain, leucine-rich repeat family pyrin domain containing 3) inflammasome plays an important role in the initiation of inflammatory responses, through the recognition of pathogen-associated molecular patterns and tumor progression, including tumor growth and metastasis. In this study, we examined the effects of defective NLRP3 on the growth, migration, and invasiveness of hepatocellular carcinoma (HCC) SK-Hep1 cell. First, HCC SK-Hep1 cells were transfected with human NLRP3 targeting LentiCRISPRv2 vector using the CRISPR-Cas9 system, and NLRP3 deficiency was confirmed by RT-qPCR and western blotting. NLRP3 deficient SK-Hep1 cells showed delayed cell growth and decreased protein expression of PI3K, p-AKT, and pNF-κB when compared to NLRP3 complete SK-Hep1 cells. In addition, NLRP3 deficiency arrested the cell cycle at G1 phase through an increase in p21 and a reduction in CDK6. NLRP3 deficient SK-Hep1 cells also showed significantly delayed cell migration, invasion, and wound healing. The expression of epithelial-mesenchymal transition signaling molecules, such as N-cadherin and MMP-9, was found to be dramatically decreased in NLRP3 deficient SK-Hep1 cells compared to NLRP3 complete SK-Hep1 cells.

• Korean Journal of Pharmacognosy
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• v.38 no.2 s.149
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• pp.176-180
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• 2007

Five liglans, sauchinone (1), di-0-methyltetrahydrofuriguaiacin B (2), manassantin A (3), manassantin B (4) and saucerneol B (5), have been isolated from the MeOH extract of Saururus chinesis roots. The evaluation for protective effect of compounds 1-5 against tacrine-induced cytotoxicity in human liver-derived Hep G2 cells was conducted. Compounds 1,2, and 5 showed significant protective effects with the EC$_{50}$ values of74.2${\pm}$0.9, 111.3${\pm}$0.8,64.3${\pm}$0.8 ${\mu}$M, respectively. Silybin, one of the well-known hepatoprotective agents, used as a positive control, and also showed protective effect with an EC$_{50}$ value of 86.2${\pm}$0.5 ${\mu}$M.

• YAKHAK HOEJI
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• v.59 no.5
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• pp.201-206
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• 2015

The aim of the present study was to optimize in vitro method for the prediction of drug-induced liver injury using human liver microsomes (HLM). Cytotoxicity test of cyclophosphamide and acetaminophen in HepG2 cells cultured with HLM showed that the newly established condition using 0.375 mg/ml HLM for 24 hr incubation was comparable or more sensitive than the previously established condition using 0.75 mg/ml HLM for 12 hr incubation. Although the cytotoxic effect of troglitazone was completely attenuated by 0.75 mg/ml HLM, it was augmented by 0.375 mg/ml HLM in the presence of the NADPH-generating system. The cytotoxic effect of chlormezanone, a withdrawn drug due to hepatotoxicity in human, was increased by HLM in the presence of the NADPH-generating system. In contrast, the cytotoxic effect of methapyrilene, a withdrawn drug due to hepatotoxicity in rats, was decreased by HLM in the presence of the NADPH-generating system. The present study suggests that the optimized in vitro method using HLM can be useful for the prediction of drug-induced hepatotoxicity.

• 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.25 no.4
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• pp.441-449
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• 2015

Endlicheria anomala, a neotropical plant, is found in northern South America and the Amazon region. It is traditionally used to remove poisons and cure gangrene. According to recent data, this plant has diverse biological properties such as anti-oxidative, anti-inflammatory and anti-melanogenic properties. However, the anti-cancer effect of E. anomala and its molecular mechanisms remain unclear. In this study, we examined the anti-cancer effect and the active mechanism of methanol extract of E. anomala (MEEA) in human lung adenocarcinoma cells (A549) and human liver cancer cells (HepG2). Our data revealed that MEEA showed cytotoxic activity in a dose-dependent manner and induced apoptosis both in A549 and HepG2 cells. We verified evidences of apoptosis via formation of chromatin condensation, apoptotic body and accumulation of cells in the subG1 phase. Following observed apoptosis-related phenomena, we found that the induction of apoptosis by MEEA was associated with the increase of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. Furthermore, MEEA-induced apoptosis was characterized with proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of pro-apoptotic Bax expression. Taken together, these findings indicate that MEEA may have potential cancer therapeutic utility in A549 and HepG2 cells.

• Journal of Life Science
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• v.10 no.1
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• pp.79-85
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• 2000

Chemoprevention is one of the major strategies for cancer control. It is well established that dietary factors play an important role in modulating the development of certain types of human cancer. The experiment was conducted to determine quinone reductase(QR) activity induction of Daucus carota L. on HepG2 cells. Among various partition layers of roots of Daucus carota L., the ethyl acetate partition layer(DCMEA) and the n-hexane partition layer(DCMH) tested to be most effective which resulted 2.1 and 1.6 respectively compared to the control value of 1.0. In the case of seeds of Daucus carota L. n-butanol partition layer (DCMB) on HepG2 cells at a dose of 200 $\mu\textrm{g}$/$m\ell$ showed the highest induction activity of QR which was 3.0. These results suggest that potentially useful cancer chemoprevention chemicals could be isolated from DCMEA and DCMH of the roots and DCMB of the seeds of Daucus carota L.

• 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 the Korean Society of Food Science and Nutrition
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• v.30 no.1
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• pp.86-91
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• 2001

The anticarcinogenic effects of various food components on human cancer cells have received much attention in recent years. The precise effect and mechanisms of anticarcinogens in food materials on cancer cells have rarely been investigated. This study was carried out to determine the effects of Daucus carota L. leaf (DCL) extracts on cytotoxic and chemopreventive effect on human cancer cells. The experiment was conducted to determine cytotoxicity of Daucus carota L. leaf extracts on HepG2, Hela and MCF-7 cells by MTT assay. Among various partition layers of Daucus carota L. leaf, the ethylacetate partition layer (DCLMEA) at 500 $\mu\textrm{g}$/mL was shown to be most effective on MCF-7 cell lines. The four partition layers which are DCLM, DCLMH, DCLMB and DCLMH were less effecitve in inducing cytotoxicity than DCLMEA was. We also determined the induction of intracellular quinone reductase (QR) activity by adding DCL extracts on HepG2 cells. Among various partition layers of DCL extracts, DCLMH and DCLM were tested to be most effective with results such as 4.9 and 4.73 with a control value of 1.0.

• Herbal Formula Science
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• v.15 no.2
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• pp.127-137
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• 2007

The purpose of this study was to investigate the effect of Yong-dam-sa-gan-tang (YST) on apoptosis in HepG2 cells, First of all. to study the cytotoxic effect of methanol extract of YST on HepG2 cells, the cells were treated with various concentrations of YST and then cell viability was determined by XTT reduction method and trypan blue exclusion assay. YST reduced proliferation of HepG2 cells in a dose-dependent manner. To confirm the induction of apoptosis, HepG2 cells were treated with various concentrations of YST. The cleavage of poly AD P-ribose polymerase (P ARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of caspase-3, procaspase-8 and procaspase-8 were examined by western blot analysis. YST decreased procaspase-3, procaspase-8 and procaspase-9 levels in a dose-dependent manner and induced the clevage of PARP. YST triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome c from mitochondria to cytosol. Furthermore, YST also downregulated the anti-apoptotic Bcl-2 and upregulated the pro-apoptotic-Bax. Therefore, this result suggest that YST induced HepG2 cell death through the mitochondrial pathway. Sustained activation of the Ras/Raf/MEK/ERK cascade in cells results in a cell cycle arrest and has been implicated in the differentiation of certain cell types, in many cases acting to promote differentiation. YST decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. These results suggest that YST is potentially useful as a chemo-therapeutic agent in HepG2.

• Biomolecules & Therapeutics
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• v.10 no.4
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• pp.287-292
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• 2002

To find new inhibitory effects from oriental drugs, Albizziae root was extracted in methanol and the extracted was stepwisely fractionated by hexane, chloroform, ethylacetate, butanol and water. In cytotoxic effect of Albizziae root fractions against cancer cell lines including human hepatoma cells(HepG2) were investigated. Expecially the butanol fraction exhibited a inhibition effects on the growth of human hepatoma cells(HepG2). It inhibited of HepG2 cells with the value of IC50. The activities of qutathione after B(a)P treatment were markedly decreased than control, but those levels were increased by the treatment of Albizziae root methanol fraction. The activity of glutathione-S-transferase after B(a)P treatment were markedly decreased than control, but those levels were increased by the treatment of Albizziae root methanol traction. Induction of phase II enzymes is a major mechanism of chemoprevention. The induction levels of quinone reductase(QR) activity in cultured murine hepatoma(Hepa IcIc7)cell by methanol extract of Albizziae root were measured. Among the tested tractions, the extracts of butanol were found to induce QR activities over 2.8 fold than control. These results suggest that Albizziae root has chemopreventive Potential by inducing QR activities and GST levels and increasing GSH