• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.22 no.3
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• pp.47-62
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• 2009

Glenditsia spina (GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. For these reasons, GS has been widely used as dermatologic agent clinically. In this study, the specific pathways of anti-proliferative effect of GS on human derived melanoma cells were identified. The molecular profile was measured using microarray technique to identify up- or down-regulated genes in SK-MEL-2 cell line. Pathway analysis was done by listing percentage of pathway involvement, and the represented pathways were obtained from KEGG. The transcription factor binding sequences were obtained by Transfac database. By the promoter analysis, up-regulated genes by GS were mainly associated with MAPK, Regulation of actin cytoskeleton, Wnt, Focal adhesion and Long term potentiation pathway. Down-regulated genes by GS were mainly associated with MAPK and Antigen processing and presentation pathway. And some of the transcription factors like Sp1 and NF-Y in up-regulated genes and Oct-1 in down-regulated genes by GS also identified.

• Biomedical Science Letters
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• v.13 no.4
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• pp.349-354
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• 2007

The purpose of this study was to examine the effect of vanillic acid on the cell viability and melanogenesis in melanocytes damaged by reactive oxygen species (ROS). The human skin melanoma cells (SK-MEL-3) were cultured with various concentrations of hydrogen peroxide $(H_2O_2)$. The cell viability for $H_2O_2$-induced cytotoxicity or vanillic acid against $H_2O_2$ was measured by XTT assay in these cultures. For the effect of vanillic acid on the melanogenesis, the tyrosinase inhibitory activity was measured by colorimetric assay at a wavelength of 490 nm, and melanin synthesis activity were assessed after cells were cultured in the media with or without various cencentrations of vanillic acid. In this study, $H_2O_2$ decreased cell viability dose- and time-dependent manners and $XTT_{50}$ was determined at a concentration of 80 ${\mu}M$, $H_2O_2$. Vanillic acid increased the cell viability dose dependently in human skin melanoma cells damaged by $H_2O_2$-induced cytotoxicity. In the tyrosinase inhibitory activity, vanillic acid supresssed tyrosinase activity in dosedependent manner, and also decreased significantly melanin synthesis activity compared with $H_2O_2$-treated group. From these results. It is suggested that $H_2O_2$-mediated cytotoxicity was highly by the toxic criteria of Borenfreund and Puerner and also, vanillic acid has the protective effect on ROS-induced cytotoxicity and melanogenesis in these cultures.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.320-326
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• 2015

The clinical benefits of oncogenic BRAF inhibitor therapies are limited by the emergence of drug resistance. In this study, we investigated the role of a negative regulator of the MAPK pathway, Spry2, in acquired resistance using BRAF inhibitor-resistant derivatives of the BRAF-V600E melanoma (A375P/Mdr). Real-time RT-PCR analysis indicated that the expression of Spry2 was higher in A375P cells harboring the BRAF V600E mutation compared with wild-type BRAF-bearing cells (SK-MEL-2) that are resistant to BRAF inhibitors. This result suggests the ability of BRAF V600E to evade feedback suppression in cell lines with BRAF V600E mutations despite high Spry2 expression. Most interestingly, Spry2 exhibited strongly reduced expression in A375P/Mdr cells with acquired resistance to BRAF inhibitors. Furthermore, the overexpression of Spry2 partially restored sensitivity to the BRAF inhibitor PLX4720 in two BRAF inhibitor-resistant cells, indicating a positive role for Spry2 in the growth inhibition induced by BRAF inhibitors. On the other hand, long-term treatment with PLX4720 induced pERK reactivation following BRAF inhibition in A375P cells, indicating that negative feedback including Spry2 may be bypassed in BRAF mutant melanoma cells. In addition, the siRNA-mediated knockdown of Raf-1 attenuated the rebound activation of ERK stimulated by PLX4720 in A375P cells, strongly suggesting the positive role of Raf-1 kinase in ERK activation in response to BRAF inhibition. Taken together, these data suggest that RAF signaling may be released from negative feedback inhibition through interacting with Spry2, leading to ERK rebound and, consequently, the induction of acquired resistance to BRAF inhibitors.

• Journal of Pharmacopuncture
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• v.14 no.3
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• pp.55-61
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• 2011

Objectives: Reactive Oxygen Species(ROS) are continuously produced at a high rate as a by-product of aerobic metabolism. Since tissue damage by free radical, ROS such as hydrogen peroxide($H_2O_2$), nitric oxide(NO) increases with age. Several lines of evidence provided that ROS appears to cause to develop aging-related various diseases such as cancer, arthritis, cardiovascular disease. In this study, we have conducted to investigate the pharmacological effects of red ginseng for the development possibility to pharmacopuncture drug sources or healthy aid foods. Methods: For our aims, it was investigated the biological activities of Red Ginseng ethanol extracts (RGEE) by measuring total polyphenol contents, total flavonoid contents, DPPH radical scavenging activity, ABTS radical scavenging activity and cell viability of MCF 10A and SK-MEL-2 in vitro with MTT assay method. Results: The total polyphenol contents of RGEE was 3.06${\pm}$0.11mg/g in 10mg/ml, the total flavonoid contents of RGEE was 1.35${\pm}$0.01mg/g in same concentration. The ABTS radical scavenging activity was about 80% and that of DPPH activity was 65% in 50mg/ml of RGEE. The cell viability of SKMEL-2, skin cancer cell line was decreased and that of MCF 10A, skin normal cell line was increased. Conclusions: We conclude that RGEE may be useful as potential functional foods or pharmacopuncture drug sources on the diseases induced by oxidant stress.

• 한국공간정보시스템학회:학술대회논문집
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• 2004.12a
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• pp.169-181
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• 2004

SK Telecom has already constructed GIMS system as the base common framework of LBS/GIS service system based on OGC(OpenGIS Consortium)'s international standard for the first mobile vector map service in 2002, But as service content appears more complex, renovation has been needed to satisfy multi-purpose, multi-function and maximum efficiency as requirements have been increased. This research is for preparation ion of GML3-based platform to upgrade service from GML2 based GIMS system. And with this, it will be possible for variety of application services to provide location and geographic data easily and freely. In GML 3.0, it has been selected animation, event handling, resource for style mapping, topology specification for 3D and telematics services for mobile LBS multimedia service. And the schema and transfer protocol has been developed and organized to optimize data transfer to MS(Mobile Stat ion) Upgrade to GML 3.0-based GIMS system has provided innovative framework in the view of not only construction but also service which has been implemented and applied to previous research and system. Also GIMS channel interface has been implemented to simplify access to GIMS system, and service component of GIMS internals, WFS and WMS, has gotten enhanded and expanded function.

• Molecules and Cells
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• v.41 no.2
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• pp.119-126
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• 2018

microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.

• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.302-310
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• 2019

Melanoma cells have been shown to respond to BRAF inhibitors; however, intrinsic and acquired resistance limits their clinical application. In this study, we performed RNA-Seq analysis with BRAF inhibitor-sensitive (A375P) and -resistant (A375P/Mdr with acquired resistance and SK-MEL-2 with intrinsic resistance) melanoma cell lines, to reveal the genes and pathways potentially involved in intrinsic and acquired resistance to BRAF inhibitors. A total of 546 differentially expressed genes (DEGs), including 239 up-regulated and 307 down-regulated genes, were identified in both intrinsic and acquired resistant cells. Gene ontology (GO) analysis revealed that the top 10 biological processes associated with these genes included angiogenesis, immune response, cell adhesion, antigen processing and presentation, extracellular matrix organization, osteoblast differentiation, collagen catabolic process, viral entry into host cell, cell migration, and positive regulation of protein kinase B signaling. In addition, using the PAN-THER GO classification system, we showed that the highest enriched GOs targeted by the 546 DEGs were responses to cellular processes (ontology: biological process), binding (ontology: molecular function), and cell subcellular localization (ontology: cellular component). Ingenuity pathway analysis (IPA) network analysis showed a network that was common to two BRAF inhibitorresistant cells. Taken together, the present study may provide a useful platform to further reveal biological processes associated with BRAF inhibitor resistance, and present areas for therapeutic tool development to overcome BRAF inhibitor resistance.

• Journal of Life Science
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• v.26 no.6
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• pp.633-639
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• 2016

Biomaterials including polymer, metal, ceramic, and composite have been widely applied for medical uses as medical fibers, artificial blood vessels, artificial joints, implants, soft tissue, and plastic surgery materials owing to their physicochemical properties. However, the biocompatibility and toxicity for film- and plate-form biomaterials is difficult to measure in mammalian cells because there is no appropriate incubation system. To solve these problems, we developed a novel mammalian cell culture system consisting of a silicone ring, top panel, and bottom panel and we applied two polymer films (PF) and one metal plate (MP). This system was based on the principal of sandwiching a test sample between the top panel and the bottom panel. Following the assembly of the culture system, SK-MEL-2 cells were seeded onto Styela Clava Tunic (SCT)-PF, NaHCO₃-added SCT (SCTN)-PF, and magnesium MP (MMP) and incubated at 37℃ for 24 hr and 48 hr. An MTT assay revealed that cell viability was maintained at a normal level in the SCT-PF culture group at 24 or 48 hr, although it rapidly decreased in the SCTN-PF culture group at 48 hr. Furthermore, the cell viability in the MMP culture group was very similar to that of the control group after incubation for 24 hr and 48 hr. Together, these results suggest the sandwich-type mammalian culture system developed here has the potential for the evaluation of the biocompatibility and toxicity of cells against PF- and MP-form biomaterials.

• Journal of Life Science
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• v.18 no.6
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• pp.884-890
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• 2008

Genistein, an isoflavone in soybean products, is a potential chemopreventive agent against various types of cancer. There are several studies documenting molecular alterations leading to cell cycle arrest at G2/M phase and induction of apoptosis; however, its mechanism of action and its molecular targets on the prostaglandin $E_2$ ($PGE_2$) production and telomere length regulation in human cancer remain unclear. In this study, we investigated the effect of genistein on the levels of cyclooxygenases (COXs) and telomere regulatory components of several human cancer cell lines (T24, human bladder carcinoma cells; U937, human leukemic cells; AGS, human stomach adenocarcinoma cells and SK-MEL-2, human skin melanoma cells). Genistein treatment resulted in the inhibition of cancer cell proliferation in a concentration-dependent manner. It was found that genistein treatment markedly decreased the levels of COX-2 mRNA and protein expression without significant changes in the expression of COX-1, which was correlated with a decrease in $PGE_2$ synthesis. Genistein treatment also partly inhibited the levels of human telomerase reverse transcriptase (hTERT) as well as human telomerase RNA (hTR) and telomerase-associated protein (TEP)-1, and the activity of telomerase. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of genistein.

• Journal of Life Science
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• v.31 no.2
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• pp.149-157
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• 2021

Prunus mume Sieb. et Zucc is widely distributed in East Asia (Korea, Japan, and China), and its fruit is often used as a medication and food material. However, because most previous studies have only investigated the state of Prunus mume fruit extract, studies on the various ways of processing this extract are still needed to increase its utilization. In this study, we evaluated the physicochemical properties and physiological activities of spray-dried Prunus mume vinegar powder (SPP). The sugar content, pH, total acidity, and moisture content of the SPP were 8.90 °Brix, 3.19, 1.05%, and 3.07%, respectively. The SPP exhibited significantly high antioxidant activity in terms of DPPH radical scavenging activity (65.55%), reducing power (1.48), and hydrogen peroxide scavenging activity (48.07%). In addition, the SPP remarkably decreased the cell viability of human breast MDA-MB-231 and human skin cancer SK-MEL-28 in a dose-dependent manner. The morphological results of the treatment of MDA-MB-231 cells with SPP were distorted, shrunken cell masses. Furthermore, apoptotic bodies and nuclear condensation formed in the SPP-treated MDA-MB-231 cells. The total polyphenol and flavonoid contents of the SPP were 59.58 ㎍/g (gallic acid equivalent) and 57.56 ㎍/g (quercetin equivalent). The results of this study indicate that SPP, which has antioxidant activity and anticancer effects, can be useful in the development of natural medicines and functional food ingredients.