• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.377-384
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• 2008

The root of Vitis labrusca, is used as a source of health promoting drug in Korean traditional medicine. It has been reported that root of Vitis labrusca has antioxidant, anti lipid peroxidation and anti-reactive nitrogen species (RNS) activities. The aim of this study was to elucidate the molecular changes of apoptotic signaling pathways in phorbol 12-myristate 13 acetate (PMA)-induced human hepatocellular carcinoma cell line (Hep G2). The root of Vitis labrusca, ethanol extract (RVLEE) was tested for cell viability on Hep G2 cell using the MTT assay. RVLEE exhibited weak cytotoxic activity. However, treatment of Hep G2 cells with RVLEE suppressed PMA-induced cell proliferation. Also, dramatic changes of cell death signals in cellular molecules such as Chk2/Cds1, CIDE-B, CLIMP-63, Bax, Bcl-xL, C-myc, Bcl-2, Bric-5, NIP-3, TRAF2 and BAR but not CIDE-B and DR4. Futhermore, our results showed that the treatment of Hep G2 cells with 25 and $50\; {\mu}g/ml$ of RVLEE suppressed PMA-induced COX-2 gene activity. These data suggest that RVLEE have inhibitory effect of cell proliferation, induction of apoptosis and, thus, may offer therapeutic potential in Hep G2.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.6
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• pp.936-940
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• 2004

Doenjang (Korean soy paste) is one of the popular soybean based fermented foods in Korea. This study investigated the growth and DNA synthesis inhibitory effect of doenjang methanol extracts on AGS human gastric adenocarcinoma cells, Hep 3B human hepatocellular carcinoma cells and HT-29 human colon cancer cells. In order to determine an anticancer effect of doenjang methanol extracts, other soybean fermented foods and original materials were compared. The treatment of doenjang methanol extracts (200 $\mu\textrm{g}$/mL) to the AGS, Hep 3B and HT-29 cancer cells inhibited the growth of cancer cells by 80%, 77% and 86%, respectively. Compared to other soybean fermented foods and original materials, doenjang methanol extracts showed the highest growth inhibitory effect on different cancer cells. In addition, doenjang methanol extracts (200 $\mu\textrm{g}$/mL) significantly inhibited DNA synthesis of AGS and Hep 3B cancer cells by 76% and 59%, respectively. These results suggested that this anticancer effect of doenjang may be due to specific active compounds, which will be newly produced during soybean fermented process and not contained in soybean.

• The Journal of Internal Korean Medicine
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• v.21 no.3
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• pp.443-452
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• 2000

Objective : This study was designed to evaluate the synergistic effect on cytotoxicity of combination with adriamycin and Palginhonhapwhajucwhan, a traditional prescription for cancer treatment in oriental medicine, in Chang, HL-60, Hep-3B and Alexander cells. Methods : We observed cell viability in Chang, HL-60, Hep-3B, and Alexander cells by crystal violet staining. Those cells were treated with various concentrations of adriamycin alone, Palginhonhapwhajucwhan alone and combination of two medications for 10 hr. On condition of $0.5{\mu}l/ml$ adriamycin alone, $15.6{\mu}l/ml$ Paljintanghapwhajucwhan alone and combination of two medications, at first, we observed colony forming of Chang and HL-60 cells. Second, we observed DNA fragmentation by agarose electrophoresis in Chang, HL-60, Hep-38 and Alexander cells. Third, we measured the catalytic activation of caspase-1, 2, 3, 6, 8, and 9 protease in Chang cells and caspase-3 protease in Chang, HL-60, Hep-3B and Alexander cells by using fluorogenic substrate. Finally, we isolated mRNA of Fas in Chang, HL-60, Hep-38 and Alexander cells and observed that Fas gene was amplified by RT-PCR Results : 1. The combination of adriamycin and Palginhonhapwhajucwhan synergistically augmented the cytotoxicity of Chang and HL-60 cells whereas did not in Hep-38 and Alexander cells. 2. Cotreatment of two drugs also markedly inhibited the colony forming ability both in Chang and HL-60 cells. 3. The cytotoxicity of these medicatons was revealed as apoptosis characterized by high molecular wight DNA fragmentaton. 4. The apoptotic cytotoxicity was mediated by activation of caspase-3 protease in Chang cells. 5. Synergistic increase in apoptotic cytotoxicity by combination of two medications was dependent on the expression of Fas in cancer cells. Conclusions : Combination of adriamycin and Palginhonhapwhajucwhan significantly augmented apoptotic cytotoxicity of Fas-positive cells such as Chang and HL-60 cells via acticaton of apoptosis signaling pathway.

• Journal of Life Science
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• v.34 no.7
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• pp.476-484
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• 2024

Although two-dimensional (2D) monolayer cell culture models are still widely used as the optimal models for anticancer activity research, three-dimensional (3D) multicellular tumor spheroid (3D MTS) models that can better approximate the tumor environment can offer an alternative to bridge the gap between in vitro and animal model studies. Isoalantolactone is among the sesquiterpene lactones found in medicinal plants, including the roots of Elecampane (Inula helenium L.), and is known to have various pharmacological activities, including anticancer activity. In this study, we investigated whether the anticancer activity of isoalantolactone observed in 2D models could be reproduced in a 3D MTS model derived from human hepatocellular carcinoma (HCC) Hep3B cells. According to our results, isoalantolactone inhibited the formation of MTSs in a manner dependent on the treatment concentration, which was accompanied by an increase in reactive oxygen species (ROS) generation. In particular, as isoalantolactone treatment and the culture time increased, the area of proliferating cells was replaced by cells in which apoptosis was induced. Additionally, in MTSs, isoalantolactone increased the expression of death-receptor-related proteins and the activity of caspase-3, and it decreased the expression of the Bax/Bcl-2 expression ratio and total poly(ADP-ribose) polymerase. However, when the production of ROS was artificially blocked, all these changes caused by isoalantolactone were attenuated and the cell survival rate of MTS cells was restored. Therefore, the results of this study suggest that the induction of apoptosis in Hep3B cell-derived MTSs by isoalantolactone is achieved through the activation of extrinsic and intrinsic pathways and is ROS-dependent.

• Journal of Life Science
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• v.21 no.11
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• pp.1549-1557
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• 2011

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in many types of transformed cells; however, some human hepatocellular carcinoma cells are particularly resistant to the effects of TRAIL. Although genistein, a natural isoflavonoid phytoestrogen, has been shown to have pro-apoptotic activity against human cancer cell lines, little is known about the mechanism of genistein in terms of TRAIL-induced apoptosis. In the present study, it was investigated whether or not combined treatment with genistein and TRAIL synergistically induced apoptosis in Hep3B hepatocarcinoma cells. Results indicate that treatment with TRAIL in combination with nontoxic concentrations of genistein sensitized TRAIL-resistant Hep3B cells to TRAIL-induced apoptosis, which was associated with mitochondrial dysfunction. Further, the inhibition of p38 mitogen-activated protein kinase (MAPK) activation markedly decreased genistein and TRAIL-induced cell viability and apoptosis by enhanced truncation of Bid, increase of pro-apoptotic Bax, decrease of anti-apoptotic Bcl-2, and release of cytochrome c from mitochondria to cytoplasm. Activation of caspases and degradation of poly (ADP-ribose) polymerase induced by the combined treatment was also markedly increased by the inhibition of p38 MAPK, through the mitochondrial amplification step. In conclusion, our data suggest that genistein sensitizes TRAIL-induced-apoptosis via p38 MAPK-dependent pathway.

• Food Science and Preservation
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• v.10 no.3
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• pp.394-400
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• 2003

This study was earned out to investigate the antimutagenic and cytotoxic effects of Eleutherococcus senticosus Maxim fruits ethanol extract on Salmonella typhimurium TA98, TA100 and cancer cell lines using Ames test and SRB assay, respectively. They were extracted with ethanol and then fractionated with hexane, chloroform, ethyl acetate, butanol and water to get active fractions. In the Ames test, most of the extracts had strong antimutagenic effects against the mutagenesis induced by MNNG, 4NQO, B(${\alpha}$)P and Trp-P-l. The ethanol extract (200 $\mu\textrm{g}$/plate) of Eleutherococcus senticosus fruits showed 87.2％ inhibitory effect on the mutagenesis induced by MNNG against TA100. And also, The suppression ratio against B(${\alpha}$)P and Trp-P-l in the TA100 showed 96.1％ and 95.5％, respectively. In the cytotoxic effects against human cancer cell lines (A549, AGS, MCF-7, Hep3B), the value of inhibition were mostly above 60％ for each fraction (1 mg/mL). Hexane fraction (1 mg/mL) against showed the strongest cytotoxic effects of 92.7％ compared to those of other fraction and butano fraetion against Hep3B was relatively high growth inhibitory effect of 82％.

• Proceedings of the Zoological Society Korea Conference
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• 1998.10b
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• pp.360-360
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• 1998

C11, a chloride-containing VK3 analog, acts as a mediator of programmed cell death in SK-Hep-1 cell lines, but its molecular mechanisms linked to cell death are not understood. In this study, we investigated the expression of p21 gene and its relationship to apoptosis induced by C11. In SK -hep-1 cells, the addition of C11 resulted in time-dependent growth suppression and DNA fragmentation characteristics of apoptosis. p21 protein was induced during this process, while the protein level of p53 was not changed at the same condition. This apoptotic cell death with p21 induction was also observed in the Hep3B cells lacking functional p53 after treatment of C11. These results suggest that C11-induced apoptosis is associated with up-regulation of p21 protein in p53-independent pathway. Next, in order to confirm whether the p53-independent p21 induction is required for C11-induced apoptosis, we introduced the p21 gene into Hep3B. Overexpression of p21 did not affect the expression of the bcl-2 gene, but DNA fragmentation and PARa cleavage were significantly increased. These data indicate that p21 is involved in C11-induced apoptosis. Although Bcl-2 has been implicated to interfere with an essential signaling molecule involved in the apoptosis pathway, its molecular mechanism and target molecule are poorly understood. To determine the effects of bcl-2 overexpression on apoptosis and to investigate whether BcI-2 interfers with the p53-independent p21 pathway, we transfected the bcl-2 expression vector into SK - Hep-1 cels. Overexpression of Bcl-2 prevented C11-induced apoptosis. Taken together, C11-induced apoptosis is regulated by p52-independent p21 pathway and bcl-2 may inhibit functional activity of p21, therebe may inhibit the C11-induced apoptosis.ptosis.

• Journal of Digital Convergence
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• v.15 no.11
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• pp.285-295
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• 2017

This study aims to provide basic data on useful functional ingredients in red ginseng by studying the anti-inflammatory and anti-cancer effects of convergence of ginsenoside Rh2(Rh2) and compound K(CK) isolated from amplified red ginseng. Therefore we examined cytotoxicity in Hep3B, activity of IL-6 induced STAT3 luciferase and survival concentration of cells in B16F10 and HaCa T. According to the experimental results, when the Rh2 and CK mixture were 10 ug/ml, there was no cytotoxicity in Hep3B cells and the anti-inflammatory effect of IL-6 reduction ratio was 102%. In addition, Rh2 and CK mixture were observed to be toxic in melanoma cell line B16F10 and HaCa T (human keratinocyte) at 50 uM. FACS(fluorescence activated cell sorting) analysis showed that annexin V was not expressed and melanoma cells and keratinocyte were desorbed and killed. It can be assumed that the mechanism of killing through this phenomenon is due to the cell death of anoikis-type, and it is necessary to study the changes of cell adhesion proteins in the future in order to clarify the cell death signal system.

• BMB Reports
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• v.46 no.10
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• pp.513-518
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• 2013

We investigated the protective effects of Gymnaster koraiensis against oxidative stress-induced hepatic cell damage. We used two different cytotoxicity models, i.e., the administration of tert-butyl hydroperoxide (t-BHP) and acetaminophen, in HepG2 cells to evaluate the protective effects of G. koraiensis. The ethyl acetate (EA) fraction of G. koraiensis and its major compound, 3,5-di-O-caffeoylquinic acid (DCQA), exerted protective effects in the t-BHP-induced liver cytotoxicity model. The EA fraction and DCQA ameliorated t-BHP-induced reductions in GSH levels and exhibited free radical scavenging activity. The EA fraction and DCQA also significantly reduced t-BHP-induced DNA damage in HepG2 cells. Furthermore, the hexane fraction of G. koraiensis and its major compound, gymnasterkoreayne B (GKB), exerted strong hepatoprotection in the acetaminophen-induced cytotoxicity model. CYP 3A4 enzyme activity was strongly inhibited by the extract, hexane fraction, and GKB. The hexane fraction and GKB ameliorated acetaminophen-induced reductions in GSH levels and protected against cell death.

• Physical Therapy Rehabilitation Science
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• v.5 no.2
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• pp.53-62
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• 2016

Objective: The aim of this systematic review was to investigate for effective strategies to improve home exercise program (HEP) adherence in vestibular rehabilitation (VR). Design: Systematic review. Methods: A systematic review was conducted to identify effective strategies used to improve HEP adherence of patients in VR. Six databases, Academic Search Premier, Cochrane Library, CINAHL, PUBMED, PsycINFO, and Web of Science were searched from their inception to December 31, 2015. The keywords used for search were 'home program', 'home intervention', 'compliance', 'adherence', 'vestibular rehabilitation', 'motion sickness', and 'motion sensitivity'. Results: A total of eight studies were selected to be included in the review. There was 95.2% agreement between the two reviewers who reviewed the studies using a quality assessment tool. The overall inter-rater agreement (${\kappa}$=0.73) showed good agreement between the reviewers. Strong evidence was identified for 3 major categories of effective HEP adherence strategies, 1) providing patient with written summary of HEP; 2) asking patient to maintain a record of HEP and symptoms; and 3) providing tele-rehabilitation in form of email and/or telephone support along with in person treatment sessions. Also, based on strong evidence, computerized technology was not found to be superior to other strategies for improving patients' HEP adherence in VR. Conclusions: The effective strategies for improving HEP in VR include written summary of exercise, maintenance of log of HEP and symptoms and tele-rehabilitation along with in person treatment sessions.