Kyeong Eun Yang

Korea Basic Science Institute KBSI, Sŏul, Seoul, South Korea

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Publications (7)17.46 Total impact

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    ABSTRACT: Phenyl-2-pyridyl ketoxime (PPKO) was found to be one of the small molecules enriched in the extracellular matrix of near-senescent human diploid fibroblasts (HDFs). Treatment of young HDFs with PPKO reduced the viability of young HDFs in a dose- and time-dependent manner and resulted in senescence-associated β-galactosidase (SA-β-gal) staining and G2/M cell cycle arrest. In addition, the levels of some senescence-associated proteins, such as phosphorylated ERK1/2, caveolin-1, p53, p16(ink4a) , and p21(waf1) , were elevated in PPKO-treated cells. To monitor the effect of PPKO on cell stress responses, reactive oxygen species (ROS) production was examined by flow cytometry. After PPKO treatment, ROS levels transiently increased at 30 min but then returned to baseline at 60 min. The levels of some antioxidant enzymes, such as catalase, peroxiredoxin II and glutathione peroxidase I, were transiently induced by PPKO treatment. SOD II levels increased gradually, whereas the SOD I and III levels were biphasic during the experimental periods after PPKO treatment. Cellular senescence induced by PPKO was suppressed by chemical antioxidants, such as N-acetylcysteine, 2,2,6,6-tetramethylpiperidinyloxy, and L-buthionine-(S,R)-sulfoximine. Furthermore, PPKO increased nitric oxide (NO) production via inducible NO synthase (iNOS) in HDFs. In the presence of NOS inhibitors, such as L-NG-nitroarginine methyl ester and L-NG-monomethylarginine, PPKO-induced transient NO production and SA-β-gal staining were abrogated. Taken together, these results suggest that PPKO induces cellular senescence in association with transient ROS and NO production and the subsequent induction of senescence-associated proteins.
    No preview · Article · Dec 2015 · Aging cell
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    ABSTRACT: Accumulative evidence suggests ginseng extract and/or its major components, ginsenosides and compound K, a metabolized ginseng saponin, have anti‑cancer effects. In the present study, the effects of a ginseng butanolic extract (GBX) and an enzymatically fortified ginseng extract (FGX), with enriched ginsenosides and compound K, on the growth of KATO3 human gastric cancer cells were investigated using a cell viability assay. While treatment with GBX at 31.25‑125 mg/ml for 24 h did not affect the proliferation of KATO3 cells, FGX under the same conditions inhibited cell proliferation in a concentration‑dependent manner. Furthermore, Annexin V/PI-staining and flow cytometric analysis demonstrated that the population of apoptotic KATO3 cells was increased following treatment with FGX, which was greater than in the GBX‑treated cells, suggesting that FGX had a stronger apoptotic effect than GBX. To investigate the underlying mechanism of the cytostatic and cytotoxic effects of the ginseng extracts, apoptosis-associated proteins were assessed using western blot analysis. The data revealed higher expression levels of B-cell lymphoma 2-associated X protein (Bax), lower expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα) and reduced phosphorylation of mammalian target of rapamycin (mTOR) and protein kinase B (PKB) in the FGX‑treated KATO3 cells than in the GBX‑treated cells. Collectively, these results demonstrated for the first time, to the best of our knowledge, that FGX had stronger anti‑proliferative and pro‑apoptotic effects on KATO3 cells than GBX. The anti‑proliferative and/or pro‑apoptotic effects of FGX appeared to be mediated via the upregulation of Bax, IκBα proteolysis (activation of nuclear factor‑κB) and the blocking of mTOR and PKB signals.
    Full-text · Article · Oct 2014 · Molecular Medicine Reports
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    ABSTRACT: Objective: To investigate the effect of three major ginsenosides from mountain ginseng as anticancer substance and explore the underlying mechanism involved in lung cancer. Methods: The inhibitory proliferation of lung cancer by major five ginsenosides (Rb1, Rb2, Rg1, Rc, and Re) was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Calculated 50% inhibition (IC50) values of five ginsenosides were determined and compared each other. Apoptosis by the treatment of single ginsenoside was performed by fluorescence-assisted cytometric spectroscopy. The alterations of apoptosis-related proteins were evaluated by Western blot analysis. Results: The abundance of ginsenosides in butanol extract of mountain ginseng (BX-MG) was revealed in the order of Rb1, Rg1, Re, Rc and Rb2. Among them, Rb1 was the most effective to lung cancer cell, followed by Rb2 and Rg1 on the basis of relative IC50 values of IMR90 versus A549 cell. The alterations of apoptotic proteins were confirmed in lung cancer A549 cells according to the administration of Rb1, Rb2 and Rg1. The expression levels of caspase-3 and caspase-8 were increased upon the treatment of three ginsenosides, however, the levels of caspase-9 and anti-apoptotic protein Bax were not changed. Conclusion: Major ginsenosides such as Rb1, Rb2 and Rg1 comprising BX-MG induced apoptosis in lung cancer cells via extrinsic apoptotic pathway rather than intrinsic mitochondrial pathway.
    Full-text · Article · Aug 2014 · Chinese Journal of Integrative Medicine
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    ABSTRACT: Crude Panax ginseng has been documented to possess hair growth activity and is widely used to treat alopecia, but the effects of ginsenoside Rg3 on hair growth have not to our knowledge been determined. The aim of the current study was to identify the molecules through which Rg3 stimulates hair growth. The thymidine incorporation for measuring cell proliferation was determined. We used DNA microarray analysis to measure gene expression levels in dermal papilla (DP) cells upon treatment with Rg3. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) in human DP cells were measured by real-time polymerase chain reaction and immunohistochemistry, respectively. We also used immunohistochemistry assays to detect in vivo changes in VEGF and 3-stemness marker expressions in mouse hair follicles. Reverse transcription polymerase chain reaction showed dose-dependent increases in VEGF mRNA levels on treatment with Rg3. Immunohistochemical analysis showed that expression of VEGF was significantly up-regulated by Rg3 in a dose-dependent manner in human DP cells and in mouse hair follicles. In addition, the CD8 and CD34 were also up-regulated by Rg3 in the mouse hair follicles. It may be concluded that Rg3 might increase hair growth through stimulation of hair follicle stem cells and it has the potential to be used in hair growth products. Copyright © 2013 John Wiley & Sons, Ltd.
    Full-text · Article · Jul 2014 · Phytotherapy Research
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    ABSTRACT: Abstract Context: Sophora flavescens Ait. (Leguminosae) has been proposed as a new whitening agent for cosmetics, because it has a strong ability to inhibit tyrosinase, a key enzyme in the formation of melanin. Objective: We conducted a study to determine whether ethanol extract of the roots of S. flavescens has the potential for use as a whitening cosmetic agent by investigating its underlying mechanisms of action. Materials and methods: To elucidate the mechanism of action of S. flavescens extract, we used DNA microarray technology. We investigated the changes in the mRNA levels of genes associated with the formation and transport of melanosomes. We also identified the formation and transport of melanosomes with immunohistochemistry and immunofluorescence analyses. Finally, the skin-whitening effect in vivo of S. flavescens extract was analyzed on human skin. Results: We found that S. flavescens extract strongly inhibited tyrosinase activity (IC50, 10.4 μg/mL). Results also showed that key proteins involved in the formation and transport of melanosomes were dramatically downregulated at both mRNA and protein level in keratinocytes exposed to S. flavescens extract. In addition, a clinical trial of a cream containing 0.05% S. flavescens extract on human skin showed it had a significant effect on skin whitening by mechanical and visual evaluation (1.14-fold). Discussion and conclusion: This study provides important clues toward understanding the effects of S. flavescens extract on the formation and transport of melanosomes. From these results, we suggest that naturally occurring S. flavescens extract might be useful as a new whitening agent in cosmetics.
    No preview · Article · Nov 2013 · Pharmaceutical Biology
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    ABSTRACT: Lactobacillus casei extract (LBX) has been reported to prevent gastric cancer, but the underlying mechanism remains unclear. The proliferation and cell death of gastric cancer KATO3 cells were examined after treatment with LBX for various times and at various doses. LBX inhibited the growth of gastric cancer cells and induced apoptosis by inactivating NF-κB promoter activity. Apoptosis induced by LBX, however, is not directly associated with the intrinsic mitochondrial pathway. Immunoblot analysis revealed that LBX decreased the expressions of NF-κB and IκB. The reduced NF-κB levels led to the decreased phosphorylation of mTOR signaling components, such as PI3K, Akt, and (p70)S6 kinase. These results showed for the first time that LBX induced apoptosis in gastric cancer cells by inhibiting NF-κB and mTOR-mediated signaling.
    No preview · Article · Apr 2012 · Integrative Cancer Therapies
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    ABSTRACT: The extracellular matrix (ECM) provides an essential structural framework for cell attachment, proliferation, and differentiation, and undergoes progressive changes during senescence. To investigate changes in protein expression in the extracellular matrix between young and senescent fibroblasts, we compared proteomic data (LTQ-FT) with cDNA microarray results. The peptide counts from the proteomics analysis were used to evaluate the level of ECM protein expression by young cells and senescent cells, and ECM protein expression data were compared with the microarray data. After completing the comparative analysis, we grouped the genes into four categories. Class I included genes with increased expression levels in both analyses, while class IV contained genes with reduced expression in both analyses. Class II and Class III contained genes with an inconsistent expression pattern. Finally, we validated the comparative analysis results by examining the expression level of the specific gene from each category using Western blot analysis and semiquantitative RT-PCR. Our results demonstrate that comparative analysis can be used to identify differentially expressed genes.
    No preview · Article · May 2011 · Moleculer Cells