• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.5
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• pp.1243-1250
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• 2003

This study was designed to elucidate the synergistic cytotoxic mechanisms of the co-treatment of adriamycin and Paljinhangahm-dan in human hepatoma malignant cancer cell line, HepG2. The combination of adriamycin and the ethanol extract of Paljinhangahm-dan synergistically augmented the cytotoxicity of Adriamycin and Paljinhangahm-dan in HepG2 cells. The cytotoxicity of two drugs was revealed as apoptosis characterized by DNA fragmentaton in agarose gel electrophoresis. The apoptotic cytotoxicity of adriamycin and Paljinhangahm-dan was accompanied by the cleavage of procaspase -3 protease and PARP. Of note, anti apoptotic Bcl2 protein was obviously decreased, but Fas was dramatically increased in HepG2 cells co-treated with Adriamycin and Paljinhangahm -dan. In addition, through 2-D gel electorphoresis, we observed that the expression levels of a lot of proteins were obviously changed by the status of drug treatments. This results suggest that the synergistic cytotoxicity of the co-treatment of adriamycin and Paljinhangahm-dan might be caused by the changes of the expression levels of a lot of proteins which play pivotal roles in cell survival or death.

• The Journal of Internal Korean Medicine
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• v.24 no.1
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• pp.113-122
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• 2003

Objective : The aim of this study was to evaluate the efficacy of Gagamchunggan-tang on anti-inflammation reaction with lipopolysaccharide (LPS)-induced HepG2 cell. Method : We examined the effects of the Gagamchunggan-tang, a traditional drug for liver inflammation, on the process of lipopolysaccharide(LPS)-induced nuclear factor-${\kappa}Bp65(NF-{\kappa}Bp65)$ activation in HepG2 cell. SDS-PAGE, Western blotting, Immunofluorescence staining were studied. Results : Immunoblot analysis showed that the level of nucleic $NF-{\kappa}Bp65$ was rapidly up-regulated and cytosolic inhibitory $I-{\kappa}B{\alpha}$ was down-regulated by LPS challenge. While Gagamchunggan-tang inhibited an increase of $NF-{\kappa}Bp65$ and degradation of $I-{\kappa}B{\alpha}$ in HepG2 cell. Besides LPS-induced expression of a group of genes, such as tumor necrosis factor-${\alpha}(TNF-{\alpha})$, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2 (COX-2), are repressed by Gagamchunggan-tang. It may be concluded that Gagamchunggan-tang attenuates the progress of LPS-induced inflammation by reduction of $NF-{\kappa}Bp65$ activation. Conclusion : The Gagamchunggan-tang would be useful as a therapeutic agent for endotoxin-induced liver disease.

• Applied Biological Chemistry
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• v.40 no.6
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• pp.577-582
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• 1997

Effects of four citrus flavonoids, hesperidin, naringin and their aglycones on phosphatidate phosphohydrolase(PAP, EC 3.1.3.3) activity were examined using isolated rat microsomes as an enzyme source. In addition, these flavonoids were tested to see whether they exert any influence on the proliferation and growth in cultured human hepatocytes HepG2 cells. Flavonoids at concentration up to $10{-4}M$ had no significant effect on the number of cells and cell proliferation by MTT cell growth assay method, whereas aglycone flavonoids, hesperetin and narigenin, at concentration of $10{-3}M$ significantly inhibited cell proliferation. Hesperetin inhibited PAP activity in a dose-dependent manner starting at concentration of $10{-5}M$. Narigenin at concentration of $10{-2}M$ inhibited PAP activity markedly, while the other flavonoids did not show any significant effect. The present study, therefore, demonstrated that aglycone flavonoids exerted portent effects on PAP activity and on cell proliferation.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.350-361
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• 2020

Background: Black ginseng (BG) is a type of Korean ginseng prepared by steaming and drying raw ginseng to improve the saponin content. This study examined the effects of BG on nonalcoholic fatty liver disease (NAFLD) in HepG2 cells and diet-induced obese mice. Methods: HepG2 cells were treated with free fatty acids to induce lipid accumulation before supplementation with BG. NAFLD-induced mice were fed different doses (0.5%, 1%, and 2%) of BG for 8 weeks. Results: BG significantly reduced lipid accumulation and expression of lipogenic genes, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, sterol regulatory element-binding protein-1c, and fatty acid synthase in HepG2 cells, and the livers of mice fed a 45% high-fat diet with 10% fructose in the drinking water (HFHF diet). BG supplementation caused a significant reduction in levels of aspartate aminotransferase and alanine aminotransferase, while antioxidant enzymes activities were significantly increased in 45% high-fat diet with 10% fructose in the drinking water diet-fed mice. Expression of proliferator-activated receptor alpha and carnitine palmitoyltransferase I were upregulated at the transcription and translation levels in both HepG2 cells and diet-induced obese mice. Furthermore, BG-induced phosphorylation of AMP-activated protein kinase and acetyl CoA carboxylase in both models, suggesting its role in AMP-activated protein kinase activation and the acetyl CoA carboxylase signaling pathway. Conclusion: Our results indicate that BG may be a potential therapeutic agent for the prevention of NAFLD.

• Journal of Life Science
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• v.29 no.9
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• pp.964-971
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• 2019

Hepatic lipid accumulation and insulin resistance increases in patients with non-alcoholic fatty liver disease. Piperine is a major compound found in black pepper (Piper nigrum) and long pepper (P. longum). Piperine has been used in fine chemical for its anti-cancer, anti-obesity, anti-diabetic, anti-inflammatory and anti-oxidant properties. However, the signaling-based mechanism of piperine and its role as an inhibitor of lipogenesis and insulin resistance in human hepatocyte cells remains ill-defined. In the present study, we explored the effects of piperine on lipid accumulation and insulin resistance, and explored the potential underlying molecular mechanisms in palmitate-treated HepG2 cells. Piperine treatment resulted in a significant reduction of triglyceride content. Furthermore, piperine treatment decreased palmitate-treated intracellular lipid deposition by inhibiting the lipogenic target genes, sterol-regulatory-element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS); whereas the expression of carnitine palmitoyl transferase (CPT-1) and phosphorylation of acetyl coenzyme A carboxylase (ACC) gene involved in fatty acid oxidation was increased. Moreover, piperine also inhibited the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307). Piperine treatment modulated palmitate-treated lipid accumulation and insulin resistance in HepG2 cells with concomitant reduction of lipogenic target genes, such as SREBP-1 and FAS, and induction of CPT-1-ACC and phosphorylation of IRS-1 (Tyr632)-Akt pathways. Therefore, piperine represents a promising treatment for the prevention of lipid accumulation and insulin resistance.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.5-9
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• 2013

Rhomboids were identified as the first intramembrane serine proteases about 10 years ago. Since then, the study of the rhomboid protease family has blossomed. Rhomboid domain containing 1 (RHBDD1), highly-expressed in human testis, contains a rhomboid domain with unknown function. In the present study, we tested the hypothesis that RHBDD1 was associated with proliferation and apoptosis in hepatocellular carcinoma using recombinant lentivirus-mediated silencing of RHBDD1 in HepG2 cells. Our results showed that down-regulation of RHBDD1 mRNA levels markedly suppressed proliferation and colony formation capacity of HepG2 human hepatoma cancer cells in vitro, and induced cell cycle arrest. We also found that RHBDD1 silencing could obviously trigger HepG2 cell apoptosis. In summary, it was demonstrated that RHBDD1 might be a positive regulator for proliferative and apoptotic characteristics of hepatocellular carcinoma.

• Journal of Microbiology and Biotechnology
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• v.18 no.3
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• pp.512-519
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• 2008

Three different polysaccharide-peptide complexes (PPC, named as Fr-I, Fr-II, and Fr-III) were produced by submerged mycelial culture of an entomopathogenic fungus Cordyceps sphecocephala, and their anticancer activities were investigated in human hepatocarcinoma (HepG2) and neuroblastoma (SK-N-SH) cells. The highest inhibitory effects of PPC on both HepG2 and SK-N-SH cells were achieved with Fr-I, whereas Fr-III with low molecular mass showed lower inhibition effects. Interestingly, the inhibitory effects of the three fractions were increased after protease digestion, suggesting that the inhibitory effects resulted mainly from the carbohydrate moiety, at least in the case of Fr-II and Fr-III, of PPC. The results of DNA fragmentation in PPC-induced apoptotic cells were confirmed by both DNA ladder assay and comet assay. Our investigation also showed that PPC-induced apoptosis of both cancer cells was associated with intracellular events including DNA fragmentation, activation of caspase-3, and modulation of Bcl-2 and Bax. We conclude that PPC has potential as a novel therapeutic agent for the treatment of both HepG2 and SK-N-SH cancer cells without any cytotoxicity against normal cells.

• Proceedings of the KIEE Conference
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• 2009.07a
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• pp.1232_1233
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• 2009

Paraquat is well-known to cause hepatotoxic responses in human and other mammal species. In solution, it forms free radicals and charge-transfer complex of which formation plays an important role in determination of its biological activity in the presence of various anions. The HepG2 cells were cultured onto a quartz crystal sensor which is possible to detect the density and a viscosity changes using the resonance frequency (F) and the resonance resistance (R). The plot of F-R diagram is able to explain the rheological change of cells onto the surface of the quartz crystal sensor. In this paper, we investigated the physical properties of the HepG2 cells cultured onto a ITO electrode of the quartz crystal sensor according to the paraquat injection at various concentrations (100 mM, 10 mM, 1 mM). We also observed the morphological changes with a micro CCD camera, simultaneously. The HepG2 cells were cultured onto the ITO electrode surface of the quartz crystal modified a collagen film in $CO_2$ incubator. After the paraquat injection, we observed the changes of the morphologies by the micro CCD camera depending on time and analyzed the physical changes of cells on the electrode surface of quartz crystal using F-R diagram. From all results, we proved the effect of paraquat at various concentrations which is led to an apoptosis such as weakening and death of the cells by oxidation and reduction reaction that were produced the superoxide anions and other free radicals.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4897-4902
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• 2014

Purpose: To investigate the anticancer effects and underlying mechanisms of parthenolide on HepG2 human hepatocellular carcinoma cells. Materials and Methods: Cell viability was assessed by MTT assay and cell apoptosis through DAPI, TUNEL staining and Western blotting. Monodansylcadaverin(MDC) and AO staining were used to detect cell autophagy. Cell proliferation was assessed by Ki67 immunofluorescence staining. Results: Parthenolide induced growth inhibition in HepG2 cells. DAPI and TUNEL staining showed that parthenolide could increase the number of apoptotic nuclei, while reducing the expression of the anti-apoptotic protein Bcl-2 and elevating the expression of related proteins, like p53, Bax, cleaved caspase9 and cleaved caspase3. Parthenolide could induce autophagy in HepG2 cells and inhibited the expression of proliferation-related gene, Ki-67. Conclusions: Parthenolide can exert anti-cancer effects by inducing cell apoptosis, activating autophagy and inhibiting cell proliferation.

• Korean Journal of Food Science and Technology
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• v.43 no.4
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• pp.432-437
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• 2011

The quality characteristics and effects on the proliferation of human hepatoma HepG2 cells due to dropwort (Oenanthe javanica) extracts naturally fermented with fructooligosaccharides were investigated. Dropwort was fermented by steeping with the same weight of oligosaccaride at room temperature for 1 year, and then stored at 4$^{\circ}C$ for 1 or 2 more years. During the fermentation periods, total flavonoid content, Hunter's color (a value), and viable cell counts decreased, but reducing sugars including glucose and fructose increased. HepG2 cell proliferation was inhibited significantly by the three extracts, but no effects were observed on Chang cells. In particular, the dropwort extract fermented for 1 year showed the highest inhibitory effect. These results demonstrate that the quality characteristics and anti-proliferative effects of dropwort were affected by fermentation period. It is concluded that dropwort extract fermented for 1 year showed the highest functional properties and quality.