• The Journal of Korean Medicine
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• v.25 no.2
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• pp.33-40
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• 2004

Objective : This study investigated the apoptotic effect and its mechanism of Radix Aconiti (RA) extract and aconitine, which is a major constituent of RA, in HepG2 human hepatoma cells. Methods : We used MTT and DNA fragmentation assay to investigate cell viability and apoptotic effect on RA extract-treated HepG2 cells. In addition, to clarify the mechanism of RA extract-induced apoptosis, we applied caspase-3 enzyme activity assay and Western blotting method on poly-(ADP-ribose) polymerase (PARP) protein expression. Results : Treatment with RA extract resulted in the decrease of cell viability, and this effect was caused from apoptosis as confirmed by discontinuous fragmentation of DNA in HepG2 cells, but aconitine did not. Also, RA extract-treated HepG2 cells induced the activation of caspase-3 enzyme activity in time- and dose-dependent manners, which was accompanied by the cleavage of 116 kD PARP to 85 kD product. Conclusions : These results suggest that the apoptotic effects of RA extract on HepG2 cells could not be explained by aconitine. Additionally, RA extract induced apoptosis in hepatoma cells through caspase-3 activation and subsequent PARP cleavage.

• The Journal of Internal Korean Medicine
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• v.28 no.4
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• pp.694-708
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• 2007

Objectives : Jageum-Jung is used as an anti-cancer agent in oriental medicine, but the mechanism by which it induces cell death in cancer cells is still unclear. The purpose of this study was to investigate the effects of Jageum-Jung on apoptosis and cell cycle arrest in HepG2 hepatoma cells. Methods : Various cancer cell lines including HepG2, C6 glioma, SH-SY5Y, PANC-1, and MCF-7 cells, were used. Apoptosis was determined by DAPI nuclei staining and flow cytometry in HepG2 cells treated with various concentrations (from 25 to 200 ${\mu}g/ml$) of $H_2O$ extract of Jageum-Jung (JGJ) for 48 hrs. Expression of cell cycle arrest mediators including Rb, p53, p21, cyclin B1, cdk4, and cyclin E proteins were measured by Western blot analysis. To estimate intracellular hydrogen peroxide levels and intracellular nitric oxide levels, HepG2 cells were stained with DCFH-DA dye and DAF dye, subjected on flow cytometric analysis. Results : 1. Jageum-Jung decreased the viability of HepG2 cells in a dose-dependent manner. 2. Jageum-Jung induced the catalytic activation of caspase-3 in HepG2 cells. 3. Jageum-Jung increased the intracellular hydrogen peroxide and NO in HepG2 cells. 4. Jageum-Jung increased the expression of Rb, p53 and p21 in HepG2 cells. 5. Jageum-Jung induced the expression of cyclin B1, cdk4, and cyclin E in HepG2 cells. Conclusions : Taken together, we suggest that Jageum-Jung exhibits cytotoxic effects on HepG2 cells, causing apoptosis and cell cycle arrest. The results showed that Jageum-Jung may do so by regulating the expression of specific target molecules that promote efficient apoptotic cell death following $G_2$/M phase arrest in a dose-dependent manner.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.89-96
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• 2000

A human hepatoma cell line, Hep G2 cells are a reliable for the study of alcohol-induced hepatotoxicity. In this study, the author investigated the effect of an aqueous extract of Asparagus $cochinchinensis_{MERRIL}$ (Liliaceae) roots (ACAE) on ethanol (EtOH)-induced cytotoxicity in Hep G2 cells. ACAE dose-dependently inhibited the EtOH-induced tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ secretion. ACAE also inhibited the EtOH and $TNF-{\alpha}-induced$ cytotoxicity. Furthermore, the author found that ACAE inhibited the $TNF-{\alpha}-induced$ apoptosis of Hep G2 cells. These results suggest that ACAE may prevent the EtOH-induced cytotoxicity through inhibition of the apoptosis of Hep G2 cells.

• Biomedical Science Letters
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• v.17 no.3
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• pp.253-260
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• 2011

Chaga mushroom (Inonotus obliquus) extract has been known to have therapeutic effects, such as anti-inflammatory, hepato-protective, anti-oxidant and anti-tumor effect. In this study, we evaluated the effects of Chaga extract on the cytotoxic actions of cisplatin in HepG2 hepatoma cells. The viability of the HepG2 cells was decreased to 10% at 3 ${\mu}M$ cisplatin and to 20% at 500 ${\mu}g$/ml Chaga extract as measured by the MTT assay. The viability of HepG2 cells co-treated with cisplatin (3 ${\mu}M$) and Chaga extract (500 ${\mu}g$/ml) was decreased to 50% in compared with the control cells. The cytotoxicity of two drugs was revealed as apoptosis characterized by the chromatic condensation, nuclear fragmentation and the cleavage of pro caspase-3 in HepG2 cells. Also, the cells treated with combination of two drugs showed synergistically the loss of mitochondrial membrane potential and increase of intracellular ROS levels. Therefore, these results suggest that the combination treatment of cisplatin and Chaga extract induces apoptotic cell death in HepG2 cells and has more potential anti-tumor effect than cisplatin alone.

• 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.

• Bulletin of the Korean Chemical Society
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• v.33 no.2
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• pp.571-574
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• 2012

In present study, CdSe quantum dots (QDs) were prepared with a novel but simple, effective and exercisable method. Nine different types of carbohydrate molecules were used to modify CdSe QDs. D-mannose (Man)-coated quantum dots were prepared for labeling human hepatoma (HepG2) cells, because of the high expression of mannose receptor (MR) on HepG2 cells. The uptake characteristics of CdSe QDs-Man were investigated in HepG2 cells. The absorption rate result of MTT assay in 48 h suggested the extremely low cytotoxicity of CdSe QDs-Man. The presence of quantum dots was confirmed with fluorescence microscopy. These results were encouraging regarding the application of QDs molecules for early detection of HepG2 cells.

• Parasites, Hosts and Diseases
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• v.61 no.4
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• pp.388-396
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• 2023

Entamoeba histolytica is an enteric tissue-invasive protozoan parasite causing amoebic colitis and liver abscesses in humans. Amoebic contact with host cells activates intracellular signaling pathways that lead to host cell death via generation of caspase-3, calpain, Ca²⁺ elevation, and reactive oxygen species (ROS). We previously reported that various NADPH oxidases (NOXs) are responsible for ROS-dependent death of various host cells induced by amoeba. In the present study, we investigated the specific NOX isoform involved in ROS-dependent death of hepatocytes induced by amoebas. Co-incubation of hepatoma HepG2 cells with live amoebic trophozoites resulted in remarkably increased DNA fragmentation compared to cells incubated with medium alone. HepG2 cells that adhered to amoebic trophozoites showed strong dichlorodihydrofluorescein diacetate (DCF-DA) fluorescence, suggesting intracellular ROS accumulation within host cells stimulated by amoebic trophozoites. Pretreatment of HepG2 cells with the general NOX inhibitor DPI or NOX2-specific inhibitor GSK 2795039 reduced Entamoeba-induced ROS generation. Similarly, Entamoeba-induced LDH release from HepG2 cells was effectively inhibited by pretreatment with DPI or GSK 2795039. In NOX2-silenced HepG2 cells, Entamoeba-induced LDH release was also significantly inhibited compared with controls. Taken together, the results support an important role of NOX2-derived ROS in hepatocyte death induced by E. histolytica.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1725-1728
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• 2015

Objective: To explore effects of paclitaxel-loaded poly lactic-co-glycolic acid (PLGA) particles on the viability of human hepatocellular carcinoma (HCC) HepG2 cells. Materials and Methods: The viability of HepG2 cells was assessed using MTT under different concentrations of prepared paclitaxel-loaded particles and paclitaxel (6.25, 12.5, 25, 50, and 100 mg/L), and apoptosis was analyzed using Hochest33342/Annexin V-FITC/PI combined with an IN Cell Analyzer 2000. Results: Paxlitaxel-loaded nanoparticles were characterized by narrow particle size distribution (158.6 nm average particle size). The survival rate of HepG2 cells exposed to paclitaxel-loaded PLGA particles decreased with the increase of concentration and time period (P<0.01 or P<0.05), the dose- and time-dependence indicating sustained release (P<0.05). Moreover, apoptosis of HepG2 cells was induced, again with an obvious dose- and time-effect relationship (P<0.05). Conclusions: Paclitaxel-loaded PLGA particles can inhibit the proliferation and induce the apoptosis of HCC HepG2 cells. This new-type of paclitaxel carrier body is easily made and has low cost, good nanoparticle characterization and sustained release. Hence, paclitaxel-loaded PLGA particles deserve to be widely popularized in the clinic.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9853-9857
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• 2014

Background: The morbidity and mortality rate of liver cancer continues to rise in China and advanced cases respond poorly to chemotherapy. Ribosomal protein L24 has been reported to be a potential therapeutic target whose depletion or acetylation inhibits polysome assembly and cell growth of cancer. Materials and Methods: Total RNA of cultured amycin-resistant and susceptible HepG2 cells was isolated, and real time quantitative RT-PCR were used to indicate differences between amycin-resistant and susceptible strains of HepG2 cells. Viability assays were used to determine amycin resistance in RPL24 transfected and control vector and null-transfected HepG2 cell lines. Results: The ribosomal protein L24 transcription level was 7.7 times higher in the drug-resistant HepG2 cells as compared to susceptible cells on quantitative RT-PCR analysis. This was associated with enhanced drug resistance as determined by methyl tritiated thymidine (3H-TdR) incorporation. Conclusions: The ribosomal protein L24 gene may have effects on drug resistance mechanisms in hepatocellular carcinoma HepG2 cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.640-646
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• 2005

This study was performed for the investigation of anticancer effects of Siegesbeckia glabrescens(SG) on HepG2 cells, a human hepatoma cell line. In the previous study, we examined the involvement of nitric oxide (NO) on anti-proliferative and apoptotic efficacy of SG in vascular smooth muscle cells. The possible mechanism of the apoptotic effects of SG was investigated in HepG2 cells. SG showed potent cytotoxic activity in HepG2 but not chang cells, liver normal cells. SG treatment caused morphological change such as cell shrinkage, nuclei condensation and cell blebbing in HepG2 cells. SG also increased the nitrite production of HepG2 cells in a dose-dependent manner. Furthermore, L-NNA treatment inhibited the anti-proliferative effect of SG. From RT-PCR, SG decreased Bcl-2 but no affected on Bax. Western blot for procaspase-3 and COX-2 showed that degradation of procaspase-3 protein level or inhibition of COX-2 protein expression by SG treatment. In addition, the apoptotic effect of SG was also demonstrated by DNA laddering. In conclusion, SG-induced HepG2 cells death can occur via apoptosis which was dose-dependent, and associated with apoptosis-related Bcl-2/Bax gene expressions, COX-2 inhibition, caspase-3 activation and NO pathway. These results suggest that SG is potentially useful as a chemotherapeutic/chemopreventive agent in hepatocellular carcinoma.