• Korean Journal of Food Science and Technology
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• v.51 no.4
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• pp.393-397
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• 2019

Proteasome inhibitors can promote apoptosis and cell cycle arrest in cancer cells by inhibition of nuclear factorkappaB ($NF-{\kappa}B$) activation. The purpose of this study was to investigate the effects of persimmon leaf extract (PSE) on proteasome activity in HepG2 human liver cancer cells. PSE treatment inhibited the proteasome activity and $NF-{\kappa}B$ activation in a dose-dependent manner in HepG2 human liver cancer cells (p<0.05). PSE treatment increased the population of cells in G2/M and sub-G1 phases. The results suggested that PSE is one of the candidate substances that may be developed into a proteasome inhibitor.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3383-3387
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• 2015

Portulaca oleracea (Family: Portulacaceae), is well known for its anti-inflammatory, antioxidative, anti-bacterial, and anti-tumor activities. However, cytotoxic effects of seed oil of Portulaca oleracea against human liver cancer (HepG2) and human lung cancer (A-549) cell lines have not been studied previously. Therefore, the present study was designed to investigate the cytotoxic effects of Portulaca oleracea seed oil on HepG2 and A-549 cell lines. Both cell lines were exposed to various concentrations of Portulaca oleracea seed oil for 24h. After the exposure, percentage cell viability was studied by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT), neutral red uptake (NRU) assays, and cellular morphology by phase contrast inverted microscopy. The results showed a concentration-dependent significant reduction in the percentage cell viability and an alteration in the cellular morphology of HepG2 and A-549 cells. The percentage cell viability was recorded as 73%, 63%, and 54% by MTT assay and 76%, 61%, and 50% by NRU assay at 250, 500, and $1000{\mu}g/ml$, respectively in HepG2 cells. Percentage cell viability was recorded as 82%, 72%, and 64% by MTT assay and 83%, 68%, and 56% by NRU assay at 250, 500, and $1000{\mu}g/ml$, respectively in A-549 cells. The 100 $100{\mu}g/ml$ and lower concentrations were found to be non cytotoxic to A-549 cells, whereas decrease of 14% and 12% were recorded by MTT and NRU assay, respectively in HepG2 cells. Both HepG2 and A-549 cell lines exposed to 250, 500, and $1000{\mu}g/ml$ of Portulaca oleracea seed oil lost their normal morphology, cell adhesion capacity, become rounded, and appeared smaller in size. The data from this study showed that exposure to seed oil of Portulaca oleracea resulted in significant cytotoxicity and inhibition of growth of the human liver cancer (HepG2) and human lung cancer (A-549) cell lines.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.10
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• pp.1514-1519
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• 2005

This study was performed to investigate the effects of Porphyra tenera (PT) on cytotoxicity and quinone reductase (QR) activity in the cancer cells. PT was extracted with methanol and further fractionated into five different types: hexane (PTMH), ethyl-ether (PTMEE), ethylacetate (PTMEA) butanol (PTMB) and aquous (PTMA) partition layers. We determined the cytotoxic effect of these layers on C6, HepG2, MCF-7, and HT-29 cell lines by MTT assay. Among the various fractions, hexane (PTMH) of PT showed the strongest cytotoxic effect on C6, HepG2 and MCF-7 cell lines. PTMH displayed very low level of cytotoxicity at the lower concentration levels and at 300 $\mu$g/mL. PTMH resulted in 87.5$\%$ growth inhibition on C6 cell 70 $\%$ on the HepG2 cell and 89$\%$ on the MCF-7 cell, which were significantly high compared to other fractions. A 400 $\mu$g/mL PTMH concentration level, 99$\%$, 94.5$\%$ and 99$\%$ of cell growth inhibition were resulted on the same cell lines. On HT-29 cell line, both hexane (PTMH) and aqueous (PTMA) fraction of PT showed cytotoxic effects, but the Percentage was not as high as previous results tested on other cell lines such as C6 HepG2 and MCF-7 cell lines. Also, we observed quinone reductase (QR) inducing-effects in all fractions of PT on HepG2 cells. The QR inducing effects of the PTMH on HepG2 cells at 150 $\mu$g/mL concentration was 6.6 times higher than the control. Although further studies are needed, the present work suggests that PT was a potential to be used as a chemopreventive.

• KSBB Journal
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• v.23 no.5
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• pp.381-386
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• 2008

Lipophilic ammonia is toxic gas and can easily diffuse across cell membranes. Excess ammonia is implicated in the pathogenesis of several metabolic disorders including hepatic encephalopathy and may result in the death. The purpose of this study was to clarify the inhibition effect of metronidazole on liver cell damage due to ammonia in human Hep G2 cell and rat hepatocytes. The effects of metronidazole were studied in ammonium chloride treated human Hep G2 cell (75 mM) and rat hepatocyte (100 mM) following $0.1{\mu}M$ metronidazole treatment. In MTZ+AC group, cell viabilities increased prominently and LDH activities decreased over 25% than AC group. Furthermore, ammonia level according to ammonium chloride treatment reduced over 30% and lipid peroxidation as an index of cell membrane damage decreased more than twice. By comparison with control, catalase activity showed more than 30% reduction in AC group while less than 10% reduction in MTZ+AC group, respectively. In addition, MTZ+AC group showed the similar cell structure as control in cell morphology study by using light microscope, and represented fluorescent intensity decrement compared with AC group in fluorescent microscopic study with avidin-TRITC fluorescent dye. And cleaved PARP expression due to ammonia reduced twofold or more in MTZ+AC group. As the results suggest, metronidazole may protect the liver cell by inhibiting cell damages due to ammonia and be used for an effective antagonist of ammonia in hyperammonemia.

• Journal of Microbiology and Biotechnology
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• v.9 no.4
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• pp.504-508
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• 1999

This report compares the selective cytotoxic effects of Doenjang fermented by various Bacillus strains (Bacillus sp. SS9, SSA3, and PM3) on human liver cell lines with that of conventional Doenjang (DTY, DTG, and DTK) and commercial Doenjang (DCM, DCD, and DCS). To investigate selective cytotoxic effects of Doenjang extracts, the cell density of HepG2 (Hepatocellular carcinoma) and CCL-13 (cells derived from human normal liver) was estimated after addition of the extracts by using a viable cell counting method. The maximum selectivity ratio ($IC_{50}$value against CCL-13/$IC_{50}$ value aganist HepG2) was observed by PM3 (extracts of Doenjang fermented with Bacillus sp. PM3). As for morphological changes shown by the addition of PM3 into HepG2 and CCL-13 cultures, HepG2 was significantly disrupted, however, CCL-13 was not affected. Also, the growth rate of HepG2 was decreased significantly by the addition of PM3. Consequently, PM3 showed a more detrimental effect on HepG2 than that on CCL-13.

• 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.27 no.1
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• pp.149-165
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• 2006

Objectives: This study was done to evaluate the effects of Saengkankunbi-tang on cell-viability, proliferation, cell-cycle, apoptosis and DNA replication on HepG2 cell and to find out by which molecular-biological mechanism by which Saengkankunbi-tang operates. Methods : The MTT assay, cell counting assay, [3H]-thymidine incorporation assay, flow cytometric analysis, tryphan blue exclusion assay, western blot analysis, quantative RT-PCR were taken. Results : Saengkankunbi-tang had no effect on proliferation, cell-cycle and DNA replications of HepG2 cells, while it improved cell viability and reduced apoptosis, and it activated Akt and NFKB. But, it did not produce an effect on cell viability and apoptosis when P13K/Akt pathway was blocked by LY294002 nor when $NF{\kapa}B$ activation was blocked by DN-$I{\kapa}B$. Conclusion : These results suggests that Saengkankunbi-tang improves cell viability and reduces apoptosis of HepG2 cells, by activating $NF{\kapa}B$ through PI3K/Akt pathway.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.384-389
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• 2014

Adiponectin, an adipokine predominantly secreted from adipose tissue, exhibits diverse biological responses, including metabolism of glucose and lipid, and apoptosis in cancer cells. Recently, adiponectin has been shown to modulate autophagy as well. While emerging evidence has demonstrated that autophagy plays a role in the modulation of proliferation and apoptosis of cancer cells, the role of autophagy in apoptosis of cancer cell caused by adiponectin has not been explored. In the present study, we demonstrated that globular adiponectin (gAcrp) induces both apoptosis and autophagy in human hepatoma cell line (HepG2 cells) and breast cancer cells (MCF-7), as evidenced by increase in caspase-3 activity, Bax, microtubule-associated protein light chain 3-II (LC3 II) protein levels, and autophagosome formation. Interestingly, gene silencing of LC3B, an autophagy marker, significantly enhanced gAcrp-induced apoptosis in both HepG2 and MCF-7 cell lines, whereas induction of autophagy by rapamycin, an mTOR inhibitor, significantly prevented gAcrp-induced apoptosis in hepatoma cells HepG2. Furthermore, modulation of autophagy produced similar effects on gAcrp-induced Bax expression in HepG2 cells. These results implicate that induction of autophagy plays a regulatory role in adiponectin-induced apoptosis of cancer cells, and thus inhibition of autophagy would be a novel promising target to enhance the efficiency of cancer cell apoptosis by adiponectin.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.5
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• pp.1251-1256
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• 2003

To determine the effect of Zibachunggan-tang(ZCT) on the process of lipopolysaccharide (LPS)-induced nuclear factor-kBp65 (NF-kBp65) activation, and LPS-induced expression of pro-inflammatory proteins including tumor necrosis factor-α (TNF-α), nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in HepG2 cell. Immunoblot analysis showed that the level of nucleic NF-kBp65 was rapidly up-regulated and cytosolic inhibitory I-kBα was down-regulated by LPS challenge. While ZCT inhibited an increase of NF-kBp65 and degradation of I-kBα in HepG2 cell. Beside LPS-induced expression of a group of genes, such as TNF-α, inducible iNOS and COX-2, are repressed by ZCT. It may be concluded that ZCT attenuates the progress of LPS-induced inflammation by reduction of NF-kBp65 activation. The ZCT would be useful as a therapeutic agent for endotoxin-induced liver disease.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.74-92
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• 2005

Objectives/Methods : To analyze the effect of Injinchunggantang(IJCGT) to Interferon-${\alpha}/{\beta}$ signal transmission system in HepG2 cells, HepG2 Cell were treated with IJCGT. Also, revelation of MxA, 2'5'-OAS mRNA leaded by Interferon-${\alpha}/{\beta}$ and revelation and activation of Jak1, TYK1, and STAT 1, all main signal transmission factors, were analyzed. Results : The analysis resulted in the following 1. With interferon ${\alpha}/{\beta}$ there was no affect cell propagation of Hep G2 cells. With IJCGT alone, cell propagation of HepG2 was promoted, and cell propagation control function was recovered. 2. With interferon ${\alpha}/{\beta}$ cell death was unaffected. With IJCGT apoptosis of HepG2 cell was restrained, and the cell's reaction to interferon was unaffected. 3. With interferon ${\alpha}/{\beta}$ treatment mRNA revelation of MxA and 2'5'-OAS was induced. When HepG2 cells were injected with IJCGT without interferon ${\alpha}/{\beta}$ treatment, mRNA revelation of MxA and 2'5'-OAS increased in proportion to the treatment density. With pre-treatment of IJCGT, leaded with interferon ${\alpha}/{\beta}$, promoted revelation of MxA, 2'5' -OAS mRNA. 4. Though mRNA revelation of lakl, TYK1 and STAT1 was unaffected with IJCGT, activation of STAT1 was promoted with an increase of phosphorylation of STAT1 protein. With pre-treatment of IJCGT, Jak1, TYK2, STAT1 phosphorylation, leaded with interferon, strengthened. 5. TNF-a, IL-1b and LPS present, revelation of MxA and 2'5'-OAS mRNA leaded by interferon was restrained when HepG2 cells were treated with IJCGT, and the interferon signal transmission system restraint action leaded by inflammatory cytokines was moderated. Conclusion : These results support a role for IJGCT in promotion of anti-virus action through maintainance of the liver's sensibility toward interferon. A clinical study of an interferon treated patient treated also with IJGCT is needed to determine its efficacy.