• Proceedings of the PSK Conference
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• 2003.10b
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• pp.107.1-107.1
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• 2003

20-O-(${\beta}$-D-Glucopyranosyl)-20(S)-protopanaxadiol (IH901), an intestinal bacterial metabolite of ginseng saponins formed from ginsenosides Rb1, Rb2 and Rc, is suggested to be a potential chemopreventive agent. Here we show that IH901 induces apoptosis in human hepatoblastoma HepG2 cells. IH901 led to an early activation of procaspase-3 (6 h posttreatment), and the activation of caspase-8 became evident only later (18 h posttreatment). Caspase activation was a necessary requirement for apoptosis because caspase inhibitors significantly inhibited cell death by IH901. (omitted)

• Journal of the Korean Society of Food Culture
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• v.39 no.3
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• pp.166-172
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• 2024

Human bitter taste-sensing type 2 receptors (hTAS2Rs) are expressed in various human tissues and may be associated with various cell signaling pathways, cell progression, and cell physiology in each tissue. hTAS2Rs can be a potential drug target because it is also expressed in some cancer cells. Xanthorrhizol (XNT) has various biological activities, such as anticancer, antimicrobial, anti-inflammatory, and antioxidant. XNT produces a bitter taste, but the specific hTAS2R activated is unknown, and the hTAS2R-mediated effect of XNT on cancer cells has not been studied. This study discovered the target receptor of XNT among 25 hTAS2Rs and confirmed the possibility of the hTAS2R-mediated inhibition of cancer cell proliferation. XNT activated only one receptor, hTAS2R38 (EC₅₀=1.606±0.021 ㎍/mL), and its activity was inhibited by probenecid, a hTAS2R38 antagonist. When HepG2 and MCF-7 cells were treated with XNT or phenylthiocarbamide (PTC), a known hTAS2R38 agonist, both chemicals inhibited cancer cell proliferation. XNT targets the human bitter taste receptor TAS2R38 and inhibits the proliferation of HepG2 and MCF-7 cells mediated by TAS2R38. This suggests that TAS2R38 may be a new target for disease treatment and a potential new factor for drug development.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.13 no.4
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• pp.391-404
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• 1991

Three anticncer agents which are different in time or dosage dependence as well as in phase specificity, namely mitomycin and adriamycin from natural products, and widely different cancer cell lines_Four epidermoid carcinomas originated from larynx, cervix, skin and gut were used toghether with one osteosarcoma as the target cell of single and combined administration of anticancer drugs. Semiautomated tetrazolium dye assay(MTT) appears to offer an attractive option for chemosensitivity of head and neck cancers since it is a simple, valid and inexpensive method of assessing chemosensitivity for large samples in a short time. The results obtained form this study were as follows. 1. Good correlations were obtained with the results of the MTT test and those of $^3H$ thymidine uptake assay. 2. $LD_{50}$ values of HIST and St.Ca. which showed relatively high doubling time on adriamycin were $30{\mu}g/ml$ and $15{\mu}g/ml$ while those of HeLa, Hep-2 and KHOS/NP were $2.1{\mu}g/ml$, $4.8{\mu}g/ml$, and $6.8{\mu}g/ml$ respectively. 3. The $LD_{50}$ value of 5-FU on five cancer cells were very high ranging from 15mg/ml to almost indefinite number, which means 5-FU is very resistant to epidermoid carcinomas or osteosarcoma examined in this study. 4. Mitomycin was relatively effective showing 80% cancer killing effect on HeLa, 70% on St. Ca. and 50% on Hep-2 at the high concentrations used. 5. Adriamycin was the most effective showing 90% cancer cell killing effect on KHOS/NP, 98% on HeLa, 80% both on Hep-2 and St. Ca. The least susceptible cancer cells toward adriamycin was HIST having only 55% cell killing effect at the high cincentration. 6. Combined therapy of adriamycin and 5-FU was more effective than single administration in all the cases examined. Most effective synergism was observed on St. Ca. at the low concentration, showing 21 times higher than each single administration.

• Journal of Applied Biological Chemistry
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• v.61 no.4
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• pp.371-377
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• 2018

The fruits of Panax ginseng were extracted with 80% aqueous MeOH and the concentrates were partitioned into EtOAc, n-BuOH, and $H_2O$ fractions. The repeated $SiO_2$ and octadecyl $SiO_2$ column chromatographies for the EtOAc fraction led to isolation of five ginsenosides. The chemical structures of these compounds were determined as ginsenoside F1 (1), ginsenoside F2 (2), ginsenoside F3 (3), ginsenoside Ia (4), notoginsenoside Fe (5) based on spectroscopic analyses including nuclear magnetic resonance, MS, and infrared. Compounds 2-5 were isolated for the first time from the fruits of P. ginseng in this study. All isolated compounds were evaluated for cytotoxic activities against human cancer cell lines such as HCT-116, SK-OV-3, human cervix adenocarcinoma (HeLa), HepG2, and SK-MEL-5. Among them compounds 2, 4, and 5 showed significant cytotoxicity on cancer cells. Compound 2 exhibited cytotoxicity on SK-MEL-5, HepG2, and HeLa cells with $IC_{50}$ values of 82.8, 86.8, and $78.3{\mu}M$, respectively. Compound 4 showed cytotoxicity on HCT-116, SK-MEL-5, SK-OV-3, HepG2, and HeLa cells with $IC_{50}$ values of 24.5, 25.4, 26.3, 22.0, and $24.9{\mu}M$, respectively. Compound 5 did on SK-MEL-5 cell with $IC_{50}$ value of $81.7{\mu}M$. The cytotoxicity of ginsenoside 2, 4, and 5 isolated from the fruits of Panax ginseng showed strong inhibition effect against on cancer cells, all of which have a glucopyranosyl moiety on C-3.

• BMB Reports
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• v.47 no.8
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• pp.433-438
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• 2014

Plant sterols have shown potent anti-proliferative effects and apoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has not been investigated. In the present study, we assessed whether the stigmasterol isolated from Navicula incerta possesses apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated the expression of pro-apoptotic gene expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2). Probably via mitochondrial apoptosis signaling pathway. With the induction of apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic cell numbers were observed through Hoechst staining, annexin V staining and cell cycle analysis. According to these results, we can suggest that the stigmasterol shows potent apoptosis inductive effects and has the potential to be tested as an anti-cancer therapeutic against liver cancer.

• Journal of Environmental Health Sciences
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• v.41 no.1
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• pp.17-23
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• 2015

Objectives: The cytotoxcities of Au, Ag, SWCNT, $SiO_2$, and ZnO nanomaterials were evaluated in order to assess their potential toxicological effects in in vitro cell models using colony forming efficiency (CFE) assay. Methods: The CFE assay of the test materials was carried out on Hep G2 cells. The size distribution of nanomaterials was studied by transmission electron microscopy (TEM). Changes in cell viability after treatment with a toxicant will result in a decreased number of colonies formed in comparison to solvent. Results: The TEM images show that all the particles except SWCNT and ZnO can be considered approximately spherical. The gold and $SiO_2$ nanoparticles show no response (no toxicity) in concentration response experiments. A statistically significant toxic effect was found in Hep G2 cells treated with Ag, SWCNT and ZnO nanomaterials. Conclusion: In this study, we considered CFE assay to be a promising test for screening studies for cytotoxicity with physicochemical analysis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.8
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• pp.1228-1235
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• 2014

We investigated the antioxidant activities and effects of soy-sprout extracts (SE) against $H_2O_2$-induced oxidative stress in HepG2 cells. The major free amino acids were asparagine, valine, pheylalanine, histidine, isoleucine, and leucine in SE. Both soy-spout extract by enzyme (SEE) and soy-spout extract by ultra high pressure (SEP) showed higher contents compared with soy-sprout water extract (SEW). The total polyphenol and isoflavone contents were highest in SEE. SEE had the highest DPPH and ABTS radical scavenging activities as well. To determine the effects of SE on $H_2O_2$-induced oxidative damage, cell viability was measured using XTT assay. Pre-treatment with SEE and SEP significantly increased cell viability compared with $H_2O_2$-treated control cells by 29% and 32%, respectively. These results indicate that SEE and SEP possess antioxidant activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3731-3736
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• 2014

Phytic acid (PA) has been reported to have positive nutritional benefits and prevent cancer formation. This study investigated the anticancer activity of rice bran PA against hepatocellular carcinoma (HepG2) cells. Cytotoxicty of PA (0.5 to 4mM) was examined by MTT and LDH assays after 24 and 48h treatment. Apoptotic activity was evaluated by expression analysis of apoptosis-regulatory genes [i.e. p53, Bcl-2, Bax, Caspase-3 and -9] by reverse transcriptase-PCR and DNA fragmentation assay. The results showed antioxidant activity of PA in Fe3+ reducing power assay ($p{\leq}0.03$). PA inhibited the growth of HepG2 cells in a concentration dependent manner ($p{\leq}0.04$). After 48h treatment, cell viability was recorded 84.7, 74.4, 65.6, 49.6, 36.0 and 23.8% in MTT assay and 92.6, 77.0%, 66.8%, 51.2, 40.3 and 32.3% in LDH assay at concentrations of 1, 1.5, 2.0, 2.5, 3.0, and 3.5mM, respectively. Hence, treatment of PA for 24h, recorded viability of cells 93.5, 88.6, 55.5, 34.6 and 24.4% in MTT assay and 94.2, 86.1%, 59.7%, 42.3 and 31.6%, in LDH assay at concentrations of 1, 2.2, 3.0, 3.6 and 4.0mM, respectively. PA treated HepG2 cells showed up-regulation of p53, Bax, Caspase-3 and -9, and down-regulation of Bcl-2 gene ($p{\leq}0.01$). At the $IC_{50}$ (2.49mM) of PA, the p53, Bax, Caspase-3 and-9 genes were up-regulated by 6.03, 7.37, 19.7 and 14.5 fold respectively. Also, the fragmented genomic DNA in PA treated cells provided evidence of apoptosis. Our study confirmed the biological activity of PA and demonstrated growth inhibition and induction of apoptosis in HepG2 cells with modulation of the expression of apoptosis-regulatory genes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5397-5402
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• 2013

The rates of morbidity and mortality of hepatocellular carcinoma (HCC) have not lessened because of difficulty in treating tumor metastasis. Mongolian Saussurea involucrata (SIE) possesses various anticancer activities, including apoptosis and cell cycle arrest. However, detailed effects and molecular mechanisms of SIE on metastasis are unclear. Thus, the present study was undertaken to investigate antimetastatic effects on HCC cells as well as possible mechanisms. Effects of SIE on the growth, adhesion, migration, aggregation and invasion of the SK-Hep1 human HCC cell line were investigated. SIE inhibited cell growth of metastatic cells in dose- and time-dependent manners. Incubation of SK-Hep1 cells with $200-400{\mu}g/mL$ of SIE significantly inhibited cell adhesion to gelatin-coated substrate. In the migration (wound healing) and aggregation assays, SIE treated cells showed lower levels than untreated cells. Invasion assays revealed that SIE treatment inhibited cell invasion capacity of HCC cells substantially. Quantitative real time PCR showed inhibitory effects of SIE on MMP-2/-9 and MT1-MMP mRNA levels, and stimulatory effects on TIMP-1, an inhibitor of MMPs. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by SIE, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 expression of SK-Hep1 cells. From these results, it was suggested that SIE could be used as potential anti-tumor agent.

• Journal of The Korean Society of Clinical Toxicology
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• v.15 no.2
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• pp.107-115
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• 2017

Purpose: Glehnia littoralis has been used to treat ischemic stroke, phlegm, cough, systemic paralysis, antipyretics and neuralgia. The pharmacological mechanisms of Glehnia littoralis include calcium channel block, coumarin derivatives, anticoagulation, anti-convulsive effect, as well as anti-oxidant and anti-inflammatory effects. Alpha-amanitin (${\alpha}$-amanitin) is a major toxin from extremely poisonous Amanita fungi. Oxidative stress, which may contribute to severe hepatotoxicity was induced by ${\alpha}$-amanitin. The aim of this study was to investigate whether Glehnia littoralis ethyl acetate extract (GLEA) has the protective antioxidant effects on ${\alpha}$-amanitin -induced hepatotoxicity. Methods: Human hepatoma cell line HepG2 cells were pretreated in the presence or absence of GLEA (50, 100 and $200{\mu}g/ml$) for 4 hours, then exposed to $60{\mu}mol/L$ of${\alpha}$-amanitin for an additional 4 hours. Cell viability was evaluated using the MTT method. AST, ALT, and LDH production in a culture medium and intracellular MDA, GSH, and SOD levels were determined. Results: GLEA (50, 100 and $200{\mu}g/ml$) significantly increased the relative cell viability by 7.11, 9.87, and 14.39%, respectively, and reduced the level of ALT by 10.39%, 34.27%, and 52.14%, AST by 9.89%, 15.16%, and 32.84%, as well as LDH by 15.86%, 22.98%, and 24.32% in culture medium, respectively. GLEA could also remarkably decrease the level of MDA and increase the content of GSH and SOD in the HepG2 cells. Conclusion: In the in vitro model, Glehnia littoralis was effective in limiting hepatic injury after ${\alpha}$-amanitin poisoning. Its antioxidant effect is attenuated by antidotal therapy.