• Food Science of Animal Resources
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• v.32 no.5
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• pp.612-617
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• 2012

The antioxidant, antimicrobial, and cytotoxic activities of ovotransferrin were investigated in vitro. The antioxidant capacity of ovotransferrin was evaluated using the 2,2-Diphenyl-1-picryl hydrazyl (DPPH) radical scavenging method, antimicrobial effects using the agar well diffusion method, and cytotoxicity using the 3-(4,5-dimethylthizol-2-yl)-2,5-diphenylatetetrazolium bromide (MTT) assay. The DPPH radical-scavenging capacity of ovotransferrin at 1 mg/mL level reached approximately 60% after 48 h of reaction. The antimicrobial effects of ovotransferrin against common food-borne pathogens, Staphylococcus aureus KCCM 32395, Bacillus cereus KCCM 40935, Listeria monocytogenes ATCC 15313, Escherichia coli O157:H7 ATCC 43895, and Helicobacter pylori HpKCTC 26695 were dose dependant. Gram-positive bacteria was more sensitive to ovotransferrin than gram-negative bacteria. Ovotransferrin showed stronger antimicrobial effect against L. monocytogenes than other gram-positive bacteria tested. The cytotoxicity of ovotransferrin was evaluated in human cancer cell lines, various tissue origins, including the larynx (Hep-2), stomach (AGS), lung (SK-MES-1), liver (HepG2), breast (MCF-7), cervix (HeLa), and colon (HT-29). Ovotransferrin displayed relatively high cytotoxicity (${\leq}60%$ inhibition effects) at 40 mg/mL. At lower concentrations (${\leq}10mg/mL$), however, ovotransferrin cytotoxic effects were not significant in all cancer cell lines tested. These results indicated that ovotransferrin has potential to be used as an antioxidant or antimicrobial agent in foods or a pharmaceutical agent against cancers.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.2
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• pp.217-222
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• 2003

We studied effects of hot water extract of Lentinus edodes (Berk.)sing. and Pleurotus eryngii (De Candolle ex Fries) Quel mushroom on proliferation and apoptosis of the human colon adenocarcinoma, HT-29 and Caco-2.. Cells were maintained with Dulbecco's modified Eagle medium/Ham's F-12 nutrient mixture supplemented with 10% fetal bovine serum at 37$^{\circ}C$ in a humidified $CO_2$. For cell proliferation experiments, cells were seeded in 35 mm dishes, treated with the various concentrations of the extract for the different time course. Apoptosis was measured by caspase-3 activity The more contents of the extract added in HT-29 and Caco-2 were, the more cell proliferation was suppressed. When we incubated HT-29 cells for 24, B\ulcorner72, and 96 hours after treatments, cell proliferation was markedly suppressed after 96 hours. Also, caspase-3 activity in HT-29 was increased by the treatment of Lentinus edodes and Pleurotus eryngii extracts. However, the treatment of the extract to SNU484, Korean stomach adenocarcinoma, did not show any influence on cell proliferation and caspase-3 activity Therefore, Lentinus edodes and Pleurotus eryngii are strongly recommended for the prevention and treatment of colon cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.1
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• pp.36-41
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• 2010

This study was conducted to investigate the effects of fermented ginseng extract by mushroom mycelia on antiproliferation of cancer cells. Phellinus linteus, Ganoderma lucidum, and Hericium erinaceum mycelia were inoculated to ginseng. The effects of fermented ginseng extract on antiproliferation of stomach (MKN-45), colon (HCT116), mammary (MCF-7), lung (NCIH460), prostate (PC-3), and liver (HepG2) cancer cells were investigated by MTT assay. Fermented ginseng extract showed significant antiproliferation effects compared with fresh ginseng extract. Fermented ginseng extract by P. linteus, G. lucidum, and H. erinaceum mycelia showed growth-inhibitory effect of 44.50, 17.75 and 43.98% viability at 1.5 mg/mL on the MKN-45 cell line, 62.86, 3.73, and 54.55% at 1.5 mg/mL on the HCT116 cell line, 41.81, 7.01, and 37.84% at 1.5 mg/mL on the MCF-7 cell line, 53.52, 5.31, and 35.27% at 1.5 mg/mL on the NCIH460 cell line, 35.05, 3.07, and 44.29% at 1.5 mg/mL on the PC-3 cell line, and 59.57, 6.34, and 4.97% at 1.5 mg/mL on the HepG2 cell line, respectively. These results indicated that fermented ginseng by G. lucidum mycelium showed the highest antiproliferation effect against various cancer cells.

• Journal of Life Science
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• v.32 no.4
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• pp.271-278
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• 2022

The detailed mechanism by which cancer upregulated gene 2 (CUG2) overexpression induces cancer stem cell-like phenotypes is not fully understood. The downregulation of FBXW7 E3 ligase, a tumor suppressor known for its proteolytic regulation of oncogenic proteins such as cyclin E, c-Myc, Notch, and Yap1, has been frequently reported in several types of tumor tissues, including those in the large intestine, cervix, and stomach. Therefore, we investigated whether FBXW7 is involved in CUG2-induced oncogenesis. In this study, the decreased expression of FBXW7 was examined in human lung adenocarcinoma A549 (A549-CUG2) and human bronchial BEAS-2B cells (BEAS-CUG2) overexpressing CUG2 and compared with control cells stably expressing an empty vector (A549-Vec or BEAS-Vec). Treatment with MG132 (a proteosome inhibitor) prevented the degradation of FBXW7 and Yap1 proteins, which are substrates of the FBXW7 E3 ligase. To address the role of Fbxw7 in the development of cancer stem cell (CSC) phenotypes, we suppressed Fbxw7 protein levels using its siRNA. We observed that decreased levels of FBXW7 enhanced cell migration, invasion, and spheroid size and number in A549-Vec and BEAS-Vec cells. The enforced expression of FBXW7 produced the opposite results in A549-CUG2 and BEAS-CUG2 cells. Furthermore, the downregulation of FBXW7 elevated the activities of EGFR, Akt, and ERK1/2 and upregulated β-catenin, Yap1, and NEK2, while the enforced expression of FBXW7 generated the opposite results. We thus propose that FBXW7 downregulation induced by CUG2 confers CSC-like phenotypes through the upregulation of both the EGFR-ERK1/2 and β-catenin-Yap1-NEK2 signaling pathways.

• Journal of Gastric Cancer
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• v.20 no.2
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• pp.212-224
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• 2020

Purpose: miR-205 is a tumor suppressor and plays an important role in tumor invasiveness. However, the role of miR-205 in human gastric cancer (GC) epithelial-mesenchymal transition (EMT) remains unclear. The aim of this study was to investigate the molecular mechanism of miR-205 in the regulation of EMT in GC invasion. Materials and Methods: Quantitative polymerase chain reaction (qPCR) was used to detect the expression of miR-205 in GC. Further, the correlation between the pathological parameters and prognosis of GC was statistically analyzed. A transwell model was used to evaluate the effect of miR-205-3p on the invasion and migration of GC cells. qPCR, western blotting, and luciferase assay were performed to analyze the relationship and target effects between miR-205-3p and the expression of zinc finger electron box binding homologous box 1 (ZEB1) and 2 (ZEB2). Results: We found that the levels of miR-205-3p were significantly lower (P<0.05) in GC tissues than in matched normal tissues. Additionally, the expression of miR-205-3p was related to the tumor invasion depth, lymph node metastasis, lymph node invasion, and tumor, node, metastasis stage. Patients with lower miR-205-3p expression levels in the tumors had a poorer prognosis. The in vitro assays indicated that miR-205-3p could affect the invasion ability and EMT of GC cells by targeting the expression of both ZEB1 and ZEB2. Conclusions: miR-205-3p promotes GC progression and affects the prognosis of patients by targeting both ZEB1 and ZEB2 to directly influence EMT.

• IMMUNE NETWORK
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• v.11 no.3
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• pp.175-181
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• 2011

Background: CM1 (centrocyte/-blast marker 1) was defined by a mAb against concavabalin-A (ConA) activated PBMC. It is expressed in germinal center of human tonsil and on the surface of activated PBMC as well as cancer cells. Recently, increased productions of pro-inflammatory mediators were detected from activated PBMC by CM1 ligation. Methods: However, there is a limitation to explain the exact role of CM1 on inflammation and its related mechanisms, since the identity of CM1 is still not clarified. In our previous study, we have already confirmed that soluble form of CM1 was produced by Raji. Therefore, we performed Q-TOF analysis after immunoprecipitation of concentrated Raji culture supernatant using anti-CM1 mAbs. Results: As a result, we found that CM1 is identical to enolase-1(ENO1), a glycolytic enzyme, and we confirmed that results by silencing ENO1 using siRNA. It was also confirmed through competition assay between anti-CM1 and anti-ENO1 mAbs. Finally, we investigated the possible role of CM1 in inflammatory response and cancer. The ligation of CM1 on Raji cells with anti-CM1 mAbs induces the extensive production of prostaglandin $E_2(PGE_2)$. In addition, the increased activity of matrix metalloproteinase (MMP)-2/9 was shown in NCI-N87, stomach cancer cell line by CM1 stimulation. Conclusion: CM1 is identical to ENO1 and it might be an important role in the regulation of inflammatory responses.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2006.02a
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• pp.83-89
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• 2006

Cellular functions are carried out by a concerted action of biochemical pathways whose components have genetic interactions. Abnormalities in the activity of the genes that constitute or modulate these pathways frequently have oncogenic implications. Therefore, identifying the upstream regulatory genes for major biochemical pathways and defining their roles in carcinogenesis can have important consequences in establishing an effective target-oriented antitumor strategy We have analyzed the gene expression profiles of human liver cancer samples using cDNA microarray chips enriched in liver and/or stomach-expressed cDNA elements, and identified groups of genes that can tell tumors from non-tumors or normal liver, or classify tumors according to clinical parameters such as tumor grade, age, and inflammation grade. We also set up a high-throughput cell-based assay system (cell chip) that can monitor the activity of major biochemical pathways through a reporter assay. Then, we applied the cell chip platform for the analysis of the HCC-associated genes discovered from transcriptome profiling, and found a number of cancer marker genes having a potential of modulating the activity of cancer-related biochemical pathways such as E2F, TCF, p53, Stat, Smad, AP-1, c-Myc, HIF and NF-kB. Some of these marker genes were previously blown to modulate these pathways, while most of the others not. Upon a fast-track phenotype analysis, a subset of the genes showed increased colony forming abilities in soft agar and altered cell morphology or adherence characteristics in the presence of purified matrix proteins. We are currently analyzing these selected marker genes in more detail for their effects on various biological Processes and for Possible clinical roles in liver cancer development.

• Journal of Gastric Cancer
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• v.1 no.2
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• pp.83-91
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• 2001

Purpose: This study was to observe whether the apoptotic function of tumor-infiltrating lymphocytes (TIL) is induced in human gastric epithelial dysplasia and gastric adenocarcinoma according to the role of FasL expression. Materials and Methods: A total of 56 gastric epithelial dysplasia and gastric adenocarcinoma patients were enrolled in this study: 9 cases of gastric epithelial dysplasia, 18 cases of early gastric carcinomas (EGC) and 29 cases of advanced gastric carcinomas (AGC). Immunohistochemical staining was performed for FasL and CD45, and the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) method was used to detect cell death in tumor-infiltrating lymphocytes. Results: 1) Positive reactions of FasL to neoplastic cells were $88.9\%$ (8/9) in gastric epithelial dysplasia, $83.3\%$ (15/18) in EGC, and $75.9\%$ (22/29) in AGC. 2) Expression of TIL was decreased in the FasL positive region and was increased in the FasL negative region, and significant expression of TIL was observed in the AGC group (P=0.001). 3) Expression of apoptotic TIL was very similar to the FasL expression, and $100\%$ expression was observed in gastric epithelial dysplasia group. 4) Expression of apoptotic TIL was increased in the FasL positive region and decreased in the FasL negative region, and significant apoptotic expression was observed in the gastric epithelial dysplasia and EGC groups (P=0.0420, P=0.0263, respectively). Conclusion: These results suggest that FasL is a prevalent mediator of immune privilege in epithelial dysplasia and cancer of the stomach.

• International Journal of Oral Biology
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• v.34 no.2
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• pp.61-72
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• 2009

Chios gum mastic (CGM) is a resin produced from the stem and leaves of Pistiacia lentiscus L var chia, a plant which grows only on Chios Island in Greece. CGM has been used for many centuries as a dietary supplement and folk medicine for stomach and duodenal ulcers in many Mediterranean countries and is known also to induce cell cycle arrest and apoptosis in some cancer cells. In this study, we further investigated the induction and mechanisms underlying the apoptotic response to CGM treatment in the SCC25 human tongue squamous cell carcinoma cell line. The viability of SCC25 cells, human normal keratinocytes (HaCaT cells) and human gingival fibroblasts (HGF-1 cells), and the growth inhibition of SCC25 cells were assessed by MTT assay and clonogenic assay, respectively. Staining with Hoechst and hemacolor dyes and TUNEL assays were employed to detect SCC25 cells undergoing apoptosis. SCC25 cells were treated with CGM, and this was followed by western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, MMP activity and proteasome activity analyses. CGM treatment of SCC25 cells was found to result in a time- and dosedependent decrease in cell viability, a dose-dependent inhibition of cell growth, and apoptotic cell death. Interestingly, CGM showed a remarkable level of cytotoxicity in SCC25 cells but not in normal cells. Tested SCC25 cells also showed several lines of apoptotic manifestation. Taken together, our present findings demonstrate that CGM strongly inhibits cell proliferation by modulating the expression of G1 cell cycle-related proteins and induces apoptosis via the proteasome, mitochondria and caspase cascades in SCC25 cells.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.51-58
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• 1993

We tried to establish the theoretical basis of clinical use of combined modality of hyperthermia and radiation therapy. For this purpose, we made an in vitro experiment in order to get the synergistic and/or additive effects on the cell killing of hyperthermia combined with radiation therapy by using the microwave-hyperthermia machine already installed at our department. In our experiment, we use two human cell lines: MKN-45 (adenocarcinoma of stomach) and K-562 (leukemia cell lines). In cases of combined treatments of hyperthermia and gamma-irradiation, the therapeutic effect was the highest in the simultaneous trial. Hyperthermia after gamma irradiation showed slightly higher therapeutic effect than that before irradiation without significant difference, but its effect was the same in the interval of 6 hours between hyperthermia and irradiation. The higher temperature and the longer treatment time were applied, the higher therapeutic effects were observed. We could observe the thermoresistance by time elapse at $43^{\circ}C$. When hyperthermia was done for 30 minutes at the same temperature, thermal enhancement ratio (TER) at DO. 01 (dose required surviving fraction of 0.01) were $2.5{\pm}0.08,\;3.75{\pm}0.18$, and $5.0{\pm}0.15\;at\;436{\circ}C,\;44^{\circ}C,\;and\;45^{\circ}C$ respectively in K-562 leukemia cell lines. Our experimental data showed that more cell killing effect can be obtained in the leukemia cell lines, although they usually are known to be radiosensitive, when treated with combined hyperthermia and radiation therapy. Furthermore, our data show that leukemia cell lines may have various intrinsic radiosensitivity, especially in vitro experiments. The magnitude of cell killing effect, however, will be less than that of MKN-45.