• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10397-10400
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• 2015

Stigmalactam, an aristolactam-type alkaloid extracted from Orophea enterocarpa, exerts cytotoxicity against several human and murine cancer cell lines, but the molecular mechanisms remain elusive. The aims of this study were to identify the mode and mechanisms of human cancer cell death induced by stigmalactam employing human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells as models, compared to normal murine fibroblasts. It was found that stigmalactam was toxic to HepG2 and MDA-MB-231 cells with $IC_{50}$ levels of $23.0{\pm}2.67{\mu}M$ and $33.2{\pm}4.54{\mu}M$, respectively, using MTT assays. At the same time the $IC_{50}$ level towards murine normal fibroblast NIH3T3 cells was $24.4{\pm}6.75{\mu}M$. Reactive oxygen species (ROS) production was reduced in stigmalactam-treated cells dose dependently after 4 h of incubation, indicating antioxidant activity, measured by using 2',7',-dichlorohydrofluorescein diacetate and flow cytometry. Caspase-3 and caspase-9 activities were increased in a dose response manner, while stigmalactam decreased the mitochondrial transmembrane potential dose-dependently in HepG2 cells, using 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, indicating mitochondrial pathway-mediated apoptosis. In conclusion, stigmalactam from O. enterocarpa was toxic to both HepG2 and MDA-MB-231 cells and induced human cancer HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway.

• Journal of Ginseng Research
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• v.36 no.3
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• pp.248-255
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• 2012

Potential antioxidant effect of processed ginseng (sun ginseng, SG) on oxidative stress generated by tert-butyl hydroperoxide (t-BHP) was investigated in HepG2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase (LDH) leakage test demonstrated that SG dose-dependently prevents a loss of cell viability against t-BHP-induced oxidative stress. Also, SG treatment dose-dependently relieved the increment of activities of hepatic enzymes, such as aspartate aminotrasferase and alanine aminotransferase, and lipid peroxidation mediated by t-BHP treatment in HepG2 cells. SG increased the gene expression of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. However, high dose of SG treatment caused decrease in mRNA level of glutathione peroxidase as compared to low dosage of SG-treated cells. The gene expression of glutathione reductase was found to be slightly increased by SG treatment. In addition, SG extract attributed its hepaprotective effect by inducing the mRNA level of bcl-2 and bcl-xL but reducing that of bax. But, the gene expression of bad showed no significant change in SG-treated HepG2 cells. These findings suggest that SG has hepatoprotective effect by showing reduction of LDH release, activities of hepatic enzymes and lipid peroxidation and regulating the gene expression of antioxidant enzymes and apoptosis-related molecules against oxdative stress caused by t-BHP in HepG2 cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.2
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• pp.329-332
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• 2002

We investigated the effect of Sarcodon aspratus extract on expression of cell cycle regulators. Methanol extract of Sarcodon aspratus showed a growth suppression on HepG2. As shown by western blot analysis, the expressions of cyclin A and Dl known as cell cycle regulators were decreased after treatment of Sarcodon aspratus extract. On the other hand, the expression of cyclin Bl was increased in the presence of Sarcodon aspratus extract. Furthermore, the expression of p53, a tumor supressor gene, and p27, a cell cycle dependent protein kinase inhibitor, were increased, whereas the expression of PCNA was decreased. In conclusion, our study suggests that growth inhibitory effect of Sardodon aspratus methanol extract on HepG2 is induced by cell cycle arrest in the Gl phase caused by decrease in cyclin A, Dl expressions and increases in p53, p27 expression.

• International Journal of Oral Biology
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• v.45 no.4
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• pp.169-178
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• 2020

L-ascorbic acid (L-AA; vitamin C) induces apoptosis in cancer cells. This study aimed to elucidate the molecular mechanisms of L-AA-induced apoptosis in human laryngeal epidermoid carcinoma Hep-2 cells. L-AA suppressed the viability of Hep-2 cells and induced apoptosis, as shown by the cleavage and condensation of nuclear chromatin and increased number of Annexin V-positive cells. L-AA decreased Bcl-2 protein expression but upregulated Bax protein levels. In addition, cytochrome c release from the mitochondria into the cytosol and activation of caspase-9, -8, and -3 were enhanced by L-AA treatment. Furthermore, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) were translocated into the nucleus during apoptosis of L-AA-treated Hep-2 cells. L-AA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation and attenuated the nuclear expression of the p65 subunit of NF-κB. Interestingly, L-AA treatment of Hep-2 cells markedly activated Akt and mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase [JNK]) and and LY294002 (Akt inhibitor), SB203580 (p38 inhibitor) or SP600125 (a JNK inhibitor) decreased the levels of Annexin V-positive cells. These results suggested that L-AA induces the apoptosis of Hep-2 cells via the nuclear translocation of AIF and EndoG by modulating the Bcl-2 family and MAPK/Akt signaling pathways.

• Herbal Formula Science
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• v.30 no.2
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• pp.67-83
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• 2022

Objectives : In this study, the anticancer activity of water extracts of three herbal medicine formulas, Bigihwan (BGH), Daechilgitang (DCGT) and Mokwhyangbinranghwan (MHBRH) listed in Donguibogam, was evaluated in HepG2 cells, a human hepatocellular carcinoma cell line. Methods : We investigated whether the cell viability of HepG2 cells was inhibited by the treatment of water extracts of three prescriptions, and whether their viability inhibitory effect was related to the induction of apoptosis. In addition, the role of autophagy on the induction of apoptosis by the treatment of these extracts was investigated. Results : The anticancer activity of the three water extracts on HepG2 cells was due to induction of apoptosis, not necrosis. Among them, BGH activated the caspase-dependent intrinsic apoptosis pathway associated with mitochondrial dysfunction. However, autophagy was induced more than 2-fold in DCGT-treated HepG2 cells, and the anticancer activity of DCGT was enhanced 1.5-fold in the presence of an autophagy inhibitor, but was attenuated in BGH and MHBRH-treated cells. Conclusion : The results of this study indicate that DCGT-induced autophagy was involved in the inhibition of apoptosis, whereas autophagy by BGH and MHBRH was related to induction of apoptosis.

• Korean Journal of Environmental Biology
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• v.31 no.4
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• pp.376-382
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• 2013

[6]-Gingerol, a major polyphenol of ginger (Zingiber officinale), exhibits a variety of biological properties including anti-oxidant, anti-inflammatory and anti-cancer activity. However, the radioprotective effect of [6]-gingerol is still unknown. The aim of this study was to investigate the radioprotective effect of [6]-gingerol against radiation-induced cell cytotoxicity and oxidative stress in HepG2 cells. [6]-Gingerol pretreatment attenuated radiation-induced cell cytotoxicity caused by 5Gy (half lethal dose, $LD_{50}$ of HepG2 cells). The measurements of superoxide dismutase (SOD) and catalase (CAT) activity were also performed. The results showed that [6]-gingerol pretreatment reduced increasing SOD and CAT activity after exposure of IR, indicating that [6]-gingerol protected oxidative stress by regulating cellular antioxidant enzyme (SOD and CAT) activity. These findings suggest that [6]-gingerol acts as a radioprotector by attenuating cell cytotoxicity and oxidative stress.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.43-43
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• 2023

In this study, we investigated in vitro inhibitory activity of wild-simulated ginseng (WSG) against non-alcoholic fatty liver disease using HepG-2 cells. T0901317 treatment increased the lipid accumulation in HepG-2 cells, but WSG treatment inhibited T0901317-mediated lipid accumulation. In addition, WSG downregulated T0901317-mediated expression of SREBP-1c, ACC, FAS and SCD-1 protein. In addition, WSG increased the phosphorylation level of LKB1 and AMPK. Compound C treatment blocked WSG-mediated downregulation of SREBP-1c protein. In conclusion, WSG is considered to inhibit the accumulation of lipids and triglycerides in HepG-2 cells by inducing the activation of LKB1 and AMPK successively, thereby reducing the expression of FAS, ACC, and SCD-1 through suppression of SREBP-1c expression.

• Preventive Nutrition and Food Science
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• v.8 no.3
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• pp.284-288
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• 2003

In this study, we investigated the effects of green tea and Pueraria radix tea on the production of Apo B$_{100}$ in Hep G$_2$ liver cells and on the expression of the low density lipoprotein (LDL) receptor. Treatment with green tea resulted in a 60.7% decrease on the Apo B$_{100}$ concentration in Hep G$_2$ cells. Pueraria radix tea decreased Apo B$_{100}$ concentration by 63.5% in Hep G$_2$ cells. Green tea and Pueraria radix tea significantly decreased Apo B$_{100}$ concentration by 64.8% and 61.8%, respectively, in the media. Treatment of the cells with green tea and Pueraria radix tea also significantly decreased the intracellular total cholesterol, but total cholesterol concentrations in the media increased by 26.4% (green tea) and 23.6% (Pueraria radix tea) above that measured in the media of control cells. The addition of green tea and Pueraria radix to the media of the Hep Gz cells increased the LDL receptor binding activities by 84.1% and 79.4%, respectively.

• 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.

• Applied Biological Chemistry
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• v.51 no.2
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• pp.129-135
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• 2008

Berberine is an isoquinoline alkaloid used in traditional Chinese medicine and has been isolated from a variety of plants, such as Coptis chinensis and Phellodendron amurense. It has a wide spectrum of clinical applications such as in anti-tumor, anti-microbial, and anti-inflammatory activities. However, it is still unknown that berberine related with reactive oxygen species (ROS)-mediated apoptosis pathway in human hepatoma HepG2 cells. In the present study, we are examined the molecular mechanism of ROS- and p38 MAP kinase-mediated apoptosis by berberine in HepG2 cells. Berberine increased cytotoxicity effects by time- and does-dependent manner. $LD_{50}$ was detected 50 ${\mu}M$ at 48h of exposure to berberine. Nuclei cleavage and apoptotic DNA fragmentation were observed in cells treated with 50 ${\mu}M$ of berberine for 48h. Moreover, berberine induced the activating of caspase-3, p53, p38 and Bax expression, whereas the expression of anti-apoptotic signaling pathways, Bcl-2, was decreased. Additionally, berberine-treated cells had an increased level of generation of ROS and nitric oxide (NO). These results indicated that berberine induces apoptosis of HepG2 cells may be mediated oxidative injury acts as an early and upstream change, triggers mitochondrial dysfunction, Bcl-2 and Bax modulation, p38 and p53 activation, caspase-3 activation, and consequent leading to apoptosis.