• Journal of Korean Neurosurgical Society
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• v.30 no.sup1
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• pp.5-12
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• 2001

This study was designed to investigate the mechanism of cell death after cisplatin treatment in human glioblastoma A172 cells. Cis-diamminedichloroplatinum(Cisplatin) demonstrated cytostatic or cytotoxic effects on A172 cells in a dosedependent manner. Cisplatin-mediated cytotoxity in A172 cells was revealed as an apoptosis characterized by high molecular weight DNA fragmentation by agarose electrophoresis as well as nuclear fragmentation by Hoechst staining. Cisplatin also resulted in the activation of caspase 3-like protease as well as poly(ADP-ribose) polymerase(PARP) cleavage. Interestingly, the anti-apoptotic Bcl2 protein was degraded and furthermore, expression of p53 protein was increased by cisplatin in a time-dependent manner. Taken together, these results suggest that anticancer drug, cisplatin induces the apoptotic death of human glioblastoma A172 cells via the activations of caspase 3-like protease, degradation of anti-apoptotic Bcl2 protein and increase in the expression of p53.

• Animal cells and systems
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• v.4 no.4
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• pp.381-388
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• 2000

Using a murine T cell hybridoma, activation-induced cell death (AICD) was studied. As an in vitro model system for the AICD, 1 cell hybridoma expressing TCR/CD3 complex was incubated onto the immobilized purified anti-CD3 antibody. The immobilized anti-CD3 antibody induced AICD effectively up to 40%. At 1-100 $\mu$M range of SNP, an exogenous source of nitric oxide (NO), the cell proliferation was not affected, but at 1 mM SNP, cell proliferation was significantly reduced. The AICD of T cell hybridoma was inhibited by exogenous NO at non-cytotoxic concentration, In the cells undergoing AICD, the expressions of caspase-3 and FasL were detected, but not iNOS. Similar result was recognized in the apoptosis induced by dexamethasone, an apoptosis-inducing agent. However, the conversion from the inactive form of caspase-3 (32 kDa) to the active form (17 kDa) was significantly reduced in the cells in AICD induced by anti-CD3 antibody, With the result of increased PARP cleavage in the cells, we propose that another PARP cleavage pathway not involving caspase-3 may function in the anti-CD3 antibody induced AICD in the T cell hybridoma.

• Journal of Pharmacopuncture
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• v.21 no.4
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• pp.268-276
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• 2018

Objectives: The purpose of this study is to investigate the anti-cancer effects of different fractions of Astragalus membranaceus (AM) in human non-small cell lung cancer (NSCLC) cells. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AM. The cell death was examined by MTT assay and trypan blue exclusion assay. Apoptosis was detected by DAPI staining, annexin V-PI double staining and cell cycle analysis. The expression of apoptosis-related proteins and mitogen-activated protein kinases (MAPKs) was examined by western blot. Results: Among various fractions of AM, the ethyl acetate fraction of AM (EAM) showed the strongest cytotoxic effect in NSCLC cells. EAM reduced the cell proliferation in a time- and dose-dependent manner in NSCLC cells. In addition, EAM induced the chromatin condensation, and increased the population of sub-G1 phase and annexin V-positive cells in a time-dependent manner, indicating that EAM induced apoptosis in NSCLC cells. Consistently, EAM enhanced the expression of cleaved caspase-8 and -9, and induced the accumulation of cleaved- poly (ADP-ribose) polymerase (PARP). Among MAPK proteins, only ERK was dephosphorylated by EAM, suggesting that ERK might be related with EAM-induced apoptosis. Conclusion: Our results clearly demonstrate that EAM exhibited anti-cancer effects in NSCLC cells by induction of apoptosis. We provide a valuable evidence which suggests that AM could be a desirable therapeutic option for treatment of NSCLC.

• International Journal of Oral Biology
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• v.44 no.2
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• pp.43-49
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• 2019

Tannic acid (TA) is a water-soluble polyphenol compound found in various herbal plants. We investigated the chemopreventive effects of TA on FaDu hypopharyngeal squamous carcinoma cells. In an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, TA showed dose-dependent cytotoxicity with a half maximal inhibitory concentration (IC50) of 50 ?M. Cell cycle analysis and immunofluorescence imaging demonstrated that under low-dose ($25{\mu}M$) treatment, FaDu cells were arrested in G2/M phase, and as the dose of TA was increased, apoptosis was induced with the increase of cell population at sub-G1 phase. The expressions of various cyclins, including cyclin D1 and cyclin-dependent kinases (CDK-1 and CDK-2), were down-regulated at low doses of TA, whereas apoptotic effectors such as cleaved caspase 3, cleaved caspase 7, and poly (ADP-ribose) polymerase (PARP) were expressed in a dose-dependent manner in Western blotting. In addition, TA-induced apoptosis of FaDu cells might be mediated by the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase pathway, with the upregulation of p-AKT/p-PKB (phosphorylated protein kinase B) and p-ERK. Overall, our data support the hypothesis that TA is a potential candidate agent for the treatment of hypopharyngeal cancer.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.158-170
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• 2018

Objectives: The objective of this study is Korean mistletoe lectin (Viscum album coloratum agglutinin, VCA) and bee venom (BV) to experimental prove comparative study of VCA and BV on the anti-cancer effect and mechanisms of action. Methods: In this study, it was examined in a human hepatocellular carcinoma cell line, Hep G2 cells. Cytotoxic effects of VCA and BV on Hep G2 cells were determined by 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay in vitro. VCA and BV killed Hep G2 cells in a time- and dose-dependent manner. Results: The apoptotic cell death was then confirmed by propidium iodide staining and DNA fragmentation analysis. The mechanisms of action was examined by the expression of anti-apoptotic proteins and activation of mitogen-activated protein kinases. Treatment of Hep G2 cells with VCA activated poly (ADP-ribose) polymerase-1 (PARP-1) known as a marker of apoptosis, and mitogen-activated protein kinases signaling pathways including SAPK/JNK, MAPK and p38. BV also activated PARP-1, MAPK, p38 but not JNK. The expression level of anti-apoptotic molecule, Bcl-X, was decreased by VCA treatment but not BV. Finally, the phosphorylation level of ERM proteins involved in the cytoskeleton homeostasis was decreased by both stimuli. Conclusion: We examined the involvement of kinase in VCA or BV - induced apoptosis by using kinase inhibitors. VCA-induced apoptosis was partially inhibited by in the presence.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.210-215
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• 2019

Colorectal cancer is one of the leading causes of cancer related death due to a poor prognosis. In this study, we investigated the effect of Gomisin G on colon cancer growth and examined the underlying mechanism of action. We found that Gomisin G significantly suppressed the viability and colony formation of LoVo cells. Gomisin G reduced the phosphorylation level of AKT implying that Gomisin G suppressed the PI3K-AKT signaling pathway. Gomisin G also induced apoptosis shown by Annexin V staining and an increased level of cleaved poly-ADP ribose polymerase (PARP) and Caspase-3 proteins. Furthermore, Gomisin G remarkably triggered the accumulation of cells at the sub-G1 phase which represents apoptotic cells. In addition, the level of cyclin D1 and phosphorylated retinoblastoma tumor suppressor protein (Rb) was also reduced by the treatment with Gomisin G thus curtailing cell cycle progression. These findings show the suppressive effect of Gomisin G by inhibiting proliferation and inducing apoptosis in LoVo cells. Taken together, these results suggest Gomisin G could be developed as a potential therapeutic compound against colon cancer.

• International Journal of Oral Biology
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• v.45 no.4
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• pp.152-161
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• 2020

D-pinitol is an analog of 3-methoxy-D-chiro-inositol found in beans and plants. D-pinitol has anti-inflammatory, antidiabetic, and anticancer effects. Additionally, D-pinitol induces apoptosis and inhibits metastasis in breast and prostate cancers. However, to date, no study has investigated the anticancer effects of D-pinitol in oral cancer. Therefore, in this study, whether the anticancer effects of D-pinitol induce apoptosis, inhibit the epithelial-to-mesenchymal transition (EMT), and arrest cell cycle was investigated in squamous epithelial cells. D-pinitol decreased the survival and cell proliferation rates of CAL-27 and Ca9-22 oral squamous carcinoma cells in a concentration- and time-dependent manner. Evidence of apoptosis, including nuclear condensation, poly (ADP-ribose) polymerase, and caspase-3 fragmentation, was also observed. D-pinitol inhibited the migration and invasion of both cell lines. In terms of EMT-related proteins, E-cadherin was increased, whereas N-cadherin, Snail, and Slug were decreased. D-pinitol also decreased the expression of cyclin D1, a protein involved in the cell cycle, but increased the expression of p21, a cyclin-dependent kinase inhibitor. Hence, D-pinitol induces apoptosis and cell cycle arrest in CAL-27 and Ca9-22 cells, demonstrating an anticancer effect by decreasing the EMT.

• The Korean Journal of Food And Nutrition
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• v.35 no.6
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• pp.464-472
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• 2022

The present study was designed to investigate the antiproliferative activity and molecular mechanisms of Bibimbap in HT-29 human colorectal adenocarcinoma cells. Bibimbap extract inhibited the proliferation of HT-29 cells by 50% at a concentration of 10.1±0.17 mg/mL for 48 h. The population of live cells decreased slightly, and the morphology changed with a reduction in cell volume (pyknosis) with Bibimbap. Treatment with 5 mg/mL of Bibimbap resulted in slight cell shrinkage. Furthermore, as the Bibimbap dose increased to 10 mg/mL, these characteristics were more evident, and HT-29 cells exhibited partial detachment by staining with the DNA-binding dye Hoechst 33342. Flow cytometric analysis by Annexin V and PI double staining showed that Bibimbap increased the levels of apoptosis. Analysis of the mechanism of these events showed that Bibimbap-treated cells exhibited a mitochondria-dependent apoptotic pathway through the modulation of caspase-3, caspase-8, caspase-9, and poly-ADP ribose polymerase, as well as Bax and Bcl-2 expression in dose- and time-dependent manners. Consequently, Bibimbap exerts a significant antiproliferative effect on HT-29 human colorectal adenocarcinoma cells.

• Journal of Marine Bioscience and Biotechnology
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• v.14 no.2
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• pp.93-101
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• 2022

Hizikia fusiforme, a type of brown algae, is widely used in Asian cuisine. It has been reported to have various pharmacological effects. In this study, the effects of the ethanol extract from H. fusiforme (EAHF) on the proliferation of human colon carcinoma cells were investigated. The effect on the survival of human hepatocarcinoma and colon carcinoma cells was examined, and results revealed that the anti-proliferative effects of EAHF were higher in colon carcinoma cells than in hepatocarcinoma cells. The inhibition of proliferation of HT29 colon carcinoma cells by EAHF treatment was closely related to the induction of apoptosis. EAHF treatment also increased caspase activity and poly(ADP-ribose) polymerase degradation, induced mitochondrial dysfunction, altered Bcl-2 family protein expression, and increased the rate of cytochrome c released from the mitochondria into the cytoplasm. Furthermore, the production of reactive oxygen species (ROS) was markedly stimulated by EAHF treatment, and when ROS production was blocked, EAHF-induced cytotoxicity was significantly attenuated. These results indicate that the anticancer activity of EAHF in HT29 colon carcinoma cells was induced by ROS-dependent mitochondrial impairment. While EAHF exhibited potent anticancer activity in colon carcinoma cells in this study, further studies on the active components of EAHF and their efficacy should be performed.

• Journal of the Korean Chemical Society
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• v.66 no.4
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• pp.298-304
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• 2022

The present study was designed to investigate the molecular mechanisms of DK-5-62, a novel (-)-catechin derivative on HCT116 human colorectal cancer cells. DK-5-62 inhibited the proliferation in dose- and time-dependent manner accompanied by the morphological changes. Effects of DK-5-62 appeared to be mediated by the induction of apoptosis, as manifested through DNA-binding dye Hoechst 33258 staining. Analysis of the mechanism of these events indicated that DK-5-62-treated cells exhibited an increased ratio of Bax/Bcl-2, resulting in the activation of caspase-9, caspase-3, and poly-ADP-ribose polymerase in a dose-dependent manner. Moreover, DK-5-62-induced apoptosis was accompanied by phosphorylation of the mitogen-activated protein kinase family, c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase. These results suggest that HCT116 cells are moderately sensitive to growth inhibition by DK-5-62 via apoptosis, as evidenced by activation of ERK/p38/Bcl-2 family signaling, as well as alteration in caspase-9 and caspase-3.