Seongnam, South Korea
Seongnam, South Korea

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Shin S.W.,Biospectrum Life Science Institute | Jung E.,Biospectrum Life Science Institute | Kim S.,Biospectrum Life Science Institute | Kim J.-H.,Dermiskin Life Science Institute | And 3 more authors.
PLoS ONE | Year: 2013

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human keratinocytes, resulting in skin inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effects of UV irradiation is essential. Therefore, in this study, we investigated the protective effects of afzelin, one of the flavonoids, against UV irradiation in human keratinocytes and epidermal equivalent models. Spectrophotometric measurements revealed that the afzelin extinction maxima were in the UVB and UVA range, and UV transmission below 376 nm was <10%, indicating UV-absorbing activity of afzelin. In the phototoxicity assay using the 3T3 NRU phototoxicity test (3T3-NRU-PT), afzelin presented a tendency to no phototoxic potential. In addition, in order to investigate cellular functions of afzelin itself, cells were treated with afzelin after UVB irradiation. In human keratinocyte, afzelin effectively inhibited the UVB-mediated increase in lipid peroxidation and the formation of cyclobutane pyrimidine dimers. Afzelin also inhibited UVB-induced cell death in human keratinocytes by inhibiting intrinsic apoptotic signaling. Furthermore, afzelin showed inhibitory effects on UVB-induced release of pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and prostaglandin-E2 in human keratinocytes by interfering with the p38 kinase pathway. Using an epidermal equivalent model exposed to UVB radiation, anti-apoptotic activity of afzelin was also confirmed together with a photoprotective effect at the morphological level. Taken together, our results suggest that afzelin has several cellular activities such as DNA-protective, antioxidant, and anti-inflammatory as well as UV-absorbing activity and may protect human skin from UVB-induced damage by a combination of UV-absorbing and cellular activities. © 2013 Shin et al.


Jung E.,Biospectrum Life Science Institute | Hwang W.,Biospectrum Life Science Institute | Kim S.,Biospectrum Life Science Institute | Kim Y.-S.,Biospectrum Life Science Institute | And 3 more authors.
Experimental Dermatology | Year: 2011

The overproduction and accumulation of melanin in the skin could lead to a pigmentary disorders, such as melasma, freckle, postinflammatory melanoderma and solar lentigo. Therefore, this study was conducted to investigate the effects of platycodin D (PD) on melanogenesis and its action mechanisms. In this study, we found that PD significantly inhibited melanin synthesis at low concentrations. These effects were further demonstrated by the PD-induced inhibition of cAMP production, phosphorylation of the cAMP-response element-binding protein and expression of microphthalmia-associated transcription factor and its downstream genes, tyrosinase, tyrosinase-related proteins-1 and Dct/tyrosinase-related proteins-2, suggesting that PD inhibits melanogenesis through the downregulation of cAMP signalling. Furthermore, PD induced significant morphological changes in melanocytes, namely, the retraction of dendrites. A small GTPase assays revealed that PD stimulated an increase in GTP-bound Rho content, one of downstream molecules of cAMP, but not in Rac or CDC42 content. Moreover, a Rho inhibitor (C3 exoenzyme) and a Rho kinase inhibitor (Y27632) attenuated the dendrite retraction induced by PD. Taken together, these findings indicate that PD inhibits melanogenesis by inhibiting the cAMP-protein kinase A pathway and also suppresses melanocyte dendricity through activation of the Rho signal that is mediated by PD-induced reduction in cAMP production. Therefore, these results suggest that PD exerts its inhibitory effects on melanogenesis and melanocyte dendricity via suppression of cAMP signalling and may be introduced as an inhibitor of hyperpigmentation caused by UV irradiation or pigmented skin disorders. © 2011 John Wiley & Sons A/S.


Lee J.,Biospectrum Life Science Institute | Lee J.,Seoul National University | Jung E.,Biospectrum Life Science Institute | Hwang W.,Biospectrum Life Science Institute | And 2 more authors.
Life Sciences | Year: 2010

Aims: Previous studies have shown that isorhamnetin has anti-adipogenic effects in mouse 3T3-L1 cells. This study was conducted to elucidate the inhibitory mechanisms of isorhamnetin during adipogenic differentiation of human adipose tissue-derived stem cells (hAMSCs). Main methods: The effect of isorhamnetin on adipogenic differentiation of hAMSCs was quantified by Oil Red O staining and a triglyceride assay. In addition, real-time PCR and Western blot were used to determine the expression of adipogenesis-related genes. Key findings: Isorhamnetin inhibited the adipocyte differentiation of hAMSCs. Additionally, when the effects of Wnt antagonists that promote adipogenesis were evaluated, isorhamnetin was found to down-regulate the mRNA levels of sFRP1 and Dkk1, but had no effect on the mRNA levels of sFRP2, sFRP3, sFRP4 and Dkk3. Isorhamnetin also inhibited the expression of Wnt receptor and co-receptor genes. Furthermore, isorhamnetin increased the protein levels of β-catenin, an effector molecule of Wnt signaling, but had no effect on the mRNA levels of β-catenin. The phosphorylation level of GSK 3β was also increased by isorhamnetin. These results were confirmed by the fact that the expression of c-myc, cyclin D1 and PPARβ, which are target genes of β-catenin, was upregulated by isorhamnetin. Moreover, isorhamnetin reduced the mRNA expression levels of C/EBPα and PPARγ which are known to be inhibited by c-myc or by cyclin D1 and PPARδ, respectively. Significance: Our results indicate that isorhamnetin inhibits the adipogenic differentiation of hAMSCs and that its mechanisms are mediated by the stabilization of β-catenin. © 2010 Elsevier Inc.


Lee J.,Korea University | Jung E.,Biospectrum Life Science Institute | Hyun J.-W.,Jeju National University | Park D.,Korea University | Park D.,Biospectrum Life Science Institute
Journal of Cellular Biochemistry | Year: 2012

Ultraviolet A (UVA) irradiation is responsible for a variety of changes in cell biology. The purpose of this study was to investigate the effects of UVA irradiation on the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs). Furthermore, we examined the UVA-antagonizing effects of L-cysteine ethylester hydrochloride (ethylcysteine) and elucidated its action mechanisms. The results of this study showed that UVA reduced the proliferative potential and stemness of hAMSCs, as evidenced by reduced proliferative activity in the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and downregulation of OCT4, NANOG, and SOX2, stemness-related genes. The mRNA level of hypoxia-inducible factor (HIF)-1α, but not HIF-2α was reduced by UVA. Moreover, the knockdown of HIF-1α using small interfering RNA (siRNA) for HIF-1α was found to downregulate stemness genes, suggesting that UVA reduces the stemness through downregulation of HIF-1α. In addition, we examined the mechanisms underlying the UVA-mediated effects and found that UVA induced production of prostaglandin (PG) E2 and 3'-5'-cyclic adenosine monophosphate (cAMP), and that this effect was mediated through activation of activating protein-1 (AP-1) and nuclear factor-κB (NF-κB). The UVA effects were antagonized by ethylcysteine, and the effects were found to be mediated by reduced production of PGE2 through the inhibition of JNK and p42/44 MAPK. Taken together, these findings show for the first time that UVA regulates the stemness of hAMSCs and its effects are mediated by downregulation of HIF-1α via the activation of PGE2-cAMP signaling. In addition, ethylcysteine may be used as an antagonizing agent to mitigate the effects of UVA. Copyright © 2012 Wiley Periodicals, Inc.


Lee J.,Korea University | Kim M.-H.,Biospectrum Life Science Institute | Lee J.-H.,Biospectrum Life Science Institute | Jung E.,Biospectrum Life Science Institute | And 2 more authors.
Journal of Cellular Biochemistry | Year: 2012

Adipocyte dysfunction is associated with the development of obesity. In this study, artemisinic acid, which was isolated from Artemisia annua L., inhibited adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSCs) and its mechanism of action was determined. The mRNA levels of peroxidase proliferation-activated receptor (PPAR) Iγ and CCAAT/enhancer binding protein (C/EBP) α, late adipogenic factors, were reduced by artemisinic acid. Moreover, the mRNA levels of the PPAR Iγ target genes lipoprotein lipase, CD36, adipocyte protein, and liver X receptor were down-regulated by artemisinic acid. Artemisinic acid reduced expression of the C/EBP β́ gene without impacting C/EBP β. In addition, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that reduced expression of the C/EBP δ gene was mediated by inhibiting Jun N-terminal kinase (JNK). Additionally, artemisinic acid also reduced the expression of the adipogenesis-associated genes glucose transporter-4 and vascular endothelial growth factor. In addition to the interference of artemisinic acid with adipogenesis, artemisinic acid significantly attenuated tumor necrosis factor-α-induced secretion of interleukin-6 by undifferentiated hAMSCs, thus influencing insulin resistance and the inflammatory state characterizing obesity. Taken together, these findings indicate that inhibiting adipogenic differentiation of hAMSCs by artemisinic acid occurs primarily through reduced expression of C/EBP δ, which is mediated by the inhibition of JNK and suggest that aremisinic acid may be used as a complementary treatment option for obesity associated with metabolic syndrome. © 2012 Wiley Periodicals, Inc.


Lee J.,Biospectrum Life Science Institute | Jung E.,Biospectrum Life Science Institute | Kim Y.-S.,Biospectrum Life Science Institute | Roh K.,Biospectrum Life Science Institute | And 2 more authors.
Journal of Biological Chemistry | Year: 2010

Adipocyte dysfunction is strongly associated with the development of obesity, which is a major risk factor for many disorders, including diabetes, hypertension, and heart disease. This study shows that ultraviolet A (UVA) inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells and its action mechanisms. The mRNA levels of peroxidase proliferator-activated receptor (PPAR) γ and CCAAT/enhancer -binding protein α (C/EBPα), but not CCAAT/enhancer-binding protein ((C/EBP) β and δ, were reduced by UVA. Moreover, the mRNA levels of PPAR γ target genes (lipoprotein lipase (LPL), CD36, adipocyte protein (aP2), and liver X receptor α (LXR)) were down-regulated by UVA. Additionally, attempts to elucidate a possible mechanism underlying the UVA-mediated effects revealed that UVA induced migration inhibitory factor (MIF) gene expression, and this was mediated through activation of AP-1 (especially JNK and p42/44 MAPK) and nuclear factor-κB. In addition, reduced adipogenesis by UVA was recovered upon the treatment with anti-MIF antibodies. AMP-activated protein kinase phosphorylation and up-regulation of Kruppel-like factor 2 (KLF2) were induced by UVA. Taken together, these findings suggest that the inhibition of adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells by UVA occurs primarily through the reduced expression of PPAR γ, which is mediated by up-regulation of KLF2 via the activation of MIF-AMP-activated protein kinase signaling. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Lee J.H.,Korea Institute of Radiological and Medical Sciences | Lee J.H.,Biospectrum Life Science Institute | Shim J.W.,Korea Institute of Radiological and Medical Sciences | Choi Y.J.,Korea Institute of Radiological and Medical Sciences | And 2 more authors.
Oncology Reports | Year: 2013

The importance of anticancer stem cell research for breast cancer lies in the possibility of providing new approaches for an improved understanding of anticancer activity and cancer treatment. In this study, we demonstrated that the preclinical therapeutic efficacy of combining the multikinase inhibitor sorafenib with radiation was more effective in hypoxia-exposed breast cancer stem cells. We assessed cell viability and Annexin V to evaluate the combined effect of sorafenib and radiation following exposure to hypoxia. Our results showed that the synergistic cytotoxicity increased tumor cell apoptosis significantly and reduced cell proliferation in MDA-MB-231 and MCF-7 cells under hypoxic conditions compared to sorafenib or radiation alone in vitro. Additionally, the combined treatment induced G2/M cell cycle arrest. Notably, the combination of sorafenib and radiation eliminated CD44+CD24 -/low cells preferentially, which highly expressed hypoxia-inducible factor (HIF)-1α and effectively inhibited primary and secondary mammosphere formation in MDA-MB-231 cells. A combined effect on MDA-MB-231 cells in response to hypoxia was shown by inhibiting angiogenesis and metastasis by suppression of HIF-1α and matrix metalloproteinase-2 (MMP-2). Collectively, these results indicate that the efficacy of sorafenib combined with radiation for treating human breast cancer cells is synergistic and suggest a new therapeutic approach to prevent breast cancer progression by eliminating breast cancer stem cells.


Kim S.,Biospectrum Life Science Institute | Jung E.,Biospectrum Life Science Institute | Kim J.-H.,Dermiskin Life Science Institute | Park Y.-H.,International University of Korea | And 2 more authors.
Food and Chemical Toxicology | Year: 2011

Although (-)-α-bisabolol, a natural monocyclic sesquiterpene alcohol, is often used as a cosmetic soothing supplement, little is known about its mechanisms of anti-inflammatory effects. Therefore, this study was designed to investigate anti-inflammatory effects of (-)-α-bisabolol and its mechanisms of action. In this study, we found that (-)-α-bisabolol inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin E 2 (PGE 2) in RAW264.7 cells. In addition, expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes was reduced, as evidenced by Western blot and luciferase reporter assays for COX-2 and iNOS. To assess the mechanism of the anti-inflammatory property of (-)-α-bisabolol, its effects on the activity of AP-1 and NF-κB promoters were examined. LPS-induced activation of AP-1 and NF-κB promoters was significantly reduced by (-)-α-bisabolol. Consistently, (-)-α-bisabolol reduced LPS-induced phosphorylation of IκBα. In addition, while LPS-induced phosphorylation of ERK and p38 was attenuated by (-)-α-bisabolol, significant changes in the level of phosphorylated JNK were not observed. Our results indicate that (-)-α-bisabolol exerts anti-inflammatory effects by downregulating expression of iNOS and COX-2 genes through inhibition of NF-κB and AP-1 (ERK and p38) signaling. © 2011.


Lee J.,Biospectrum Life Science Institute | Roh K.-B.,Biospectrum Life Science Institute | Kim S.-C.,Biospectrum Life Science Institute | Park D.,Biospectrum Life Science Institute
Journal of Nutritional Biochemistry | Year: 2012

This study was conducted to investigate the proliferative effect of vegetable soy peptides on adult stem cells (ASCs) in the absence of serum and their possible mechanisms of action. The proliferation of human adipose tissue-derived mesenchymal stem cells (ADSCs) and cord blood-derived mesenchymal stem cells (CB-MSCs) treated with soy peptides was found to increase significantly upon 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Click-iT 5-ethynyl-2'-deoxyuridine flow cytometry assay. In addition, soy peptides led to stepwise phosphorylation of the p44/42 MAPK (ERK), mammalian target of rapamycin (mTOR), p70 S6 kinase, S6 ribosomal protein (S6RP) and eukaryotic initiation factor 4E (eIF4E) in ADSCs. Furthermore, quantitative analysis of the cytokines revealed that the production of transforming growth factor-beta1 (TGF-β1), vascular endothelial growth factor and interleukin-6 increased significantly in response to treatment with soy peptides in both ADSCs and CB-MSCs. Similarly, soy peptide-induced phosphorylation of the ERK/mTOR/S6RP/eIF4E pathway was blocked in response to pretreatment with PD98059, a specific ERK inhibitor. Moreover, inhibition of TGF-β1 through PD98059 pretreatment and a consecutive decrease in ADSC proliferation revealed that TGF-β1 induces the phosphorylation of mTOR/S6RP/eIF4E. Collectively, the results of this study indicate that ERK-dependent production of TGF-β1 plays a crucial role in the soy peptide-induced proliferation of ADSCs under serum-free conditions. © 2012 Elsevier Inc.


Lee J.,Biospectrum Life Science Institute | Jung E.,Biospectrum Life Science Institute | Kim Y.-S.,Biospectrum Life Science Institute | Park D.,Biospectrum Life Science Institute | And 3 more authors.
Archives of Dermatological Research | Year: 2013

We investigated the proliferative effect of a Acanthopanax senticosus extract (ASE) on human CD49f+/CD29+ keratinocytes and isolated phloridzin from A. senticosus as an active compound. In addition, the possible mechanisms of action were examined. We found that the ASE and phloridzin-promoted proliferation of CD49f+/CD29+ cells using MTT and Click-iT™ EdU flow cytometry assays. In addition, phosphorylation of the p44/42 MAPK (ERK), mTOR, p70 S6 kinase (p70S6K), S6 ribosomal protein (S6RP), eukaryotic initiation factor 4B (eIF4B), and eIF4E was stepwise induced in CD49f+/CD29+ cells. Furthermore, the ASE and phloridzin significantly induced the production of vascular endothelial growth factor and interleukin-6 in CD49f+/CD29+ cells. Similarly, ASE and phloridzin-induced phosphorylation of the mTOR/p70S6K/S6RP/eIF4B/eIF4E pathway was blocked in response to pretreatment with PD98059, a specific ERK inhibitor. Taken together, these results indicate that ASE and phloridzin-induced proliferation of CD49f+/CD29 + cells under serum-free conditions was mediated by the ERK-dependent mTOR pathway. © 2013 Springer-Verlag Berlin Heidelberg.

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