• 제목/요약/키워드: Matrix Metalloproteinase(MMP)

검색결과 636건 처리시간 0.02초

Effect of Quercetin in the UV-Irradiated Human Keratinocyte HaCaT Cells and A Model of Its Binding To p38 MAPK

  • Jnawali, Hum Nath;Lee, Eunjung;Shin, Areum;Park, Young Guen;Kim, Yangmee
    • Bulletin of the Korean Chemical Society
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    • 제35권9호
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    • pp.2787-2790
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    • 2014
  • Quercetin is a major dietary flavonoid found in onions, apples, tea, and red wine, and potentially has beneficial effects on disease prevention. We carried out this study to investigate the effect of quercetin on UVB-induced matrix metalloproteinase-1 (MMP-1) expression in human keratinocyte HaCaT cells and to further understand the mechanisms of its action. The anti-inflammatory activity of quercetin was investigated and quercetin significantly suppressed the NO production in LPS-stimulated RAW264.7 mouse macrophages. Post treatment of quercetin decreased UV irradiation-induced phosphorylation of JNK, p38 MAPK, and ERK by 91%, 21%, and 17%, respectively. MMP-1 is mainly responsible for the degradation of dermal collagen during the aging process of human skin and quercetin suppressed the UVB-induced MMP-1 by 94%. Binding studies revealed that quercetin binds to p38 with high binding affinity ($1.85{\times}10^6M^{-1}$). The binding model showed that the 4'-hydroxy groups of the B-ring of quercetin participated in hydrogen bonding interactions with the side chains of Lys53, Glu71, and Asp168 and the 5-hydroxy group of the A-ring formed a hydrogen bond with the backbone amide of Met109. The major finding of this study shows that quercetin inhibits phosphorylation of JNK, p38 MAPK, and ERK pathway leading to the prevention of MMP-1 expression in human keratinocyte HaCaT cells. Therefore, our findings suggested the potentials of quercetin as a skin anti-photoaging agent.

Met inactivation by S-allylcysteine suppresses the migration and invasion of nasopharyngeal cancer cells induced by hepatocyte growth factor

  • Cho, Oyeon;Hwang, Hye-Sook;Lee, Bok-Soon;Oh, Young-Taek;Kim, Chul-Ho;Chun, Mison
    • Radiation Oncology Journal
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    • 제33권4호
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    • pp.328-336
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    • 2015
  • Purpose: Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. Materials and Methods: Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). Results: This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. Conclusion: These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.

Artemisinin attenuates platelet-derived growth factor BB-induced migration of vascular smooth muscle cells

  • Lee, Kang Pa;Park, Eun-Seok;Kim, Dae-Eun;Park, In-Sik;Kim, Jin Tack;Hong, Heeok
    • Nutrition Research and Practice
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    • 제8권5호
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    • pp.521-525
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    • 2014
  • BACKGROUND/OBJECTIVES: Artemisinin (AT), an active compound in Arternisia annua, is well known as an anti-malaria drug. It is also known to have several effects including anti-oxidant, anti-inflammation, and anti-cancer activities. To date, the effect of AT on vascular disorders has not been studied. In this study, we investigated the effects of AT on the migration and proliferation of vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor BB (PDGF-BB). MATERIALS/METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats. PDGF-BB stimulated VSMC migration was measured by the scratch wound healing assay and the Boyden chamber assay. Cell viability was determined by using an EZ-Cytox Cell Viability Assay Kit. The production of reactive oxygen species (ROS) in PDGF-BB stimulated VSMC was measured through $H_2DCF$-DA staining. We also determined the expression levels of signal proteins relevant to ROS, including measures of extracellular signal-regulated kinase (ERK) 1/2 measured by western blot analysis and matrix metalloproteinase (MMP) 9 measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: AT ($10{\mu}M$ and $30{\mu}M$) significantly reduced the proliferation and migration of PDGF-BB stimulated VSMC in a dose-dependent manner. The production of ROS, normally induced by PDGF-BB, is reduced by treatment with AT at both concentrations. PDGF-BB stimulated VSMC treated with AT ($10{\mu}M$ and $30{\mu}M$) have reduced phosphorylation of ERK1/2 and inhibited MMP9 expression compared to untreated PDGF-BB stimulated VSMC. CONCLUSIONS: We suggest, based on these results, that AT may exert an anti-atherosclerotic effect on PDGF-BB stimulated VSMCs by inhibiting their proliferation and migration through down-regulation of ERK1/2 and MMP9 phosphorylation.

Antioxidant Activity and Anti-wrinkle Effects of Aceriphyllum rossii Leaf Ethanol Extract

  • Ha, Bi Gyeon;Park, Min Ah;Lee, Chae Myoung;Kim, Young Chul
    • Toxicological Research
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    • 제31권4호
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    • pp.363-369
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    • 2015
  • We evaluated the antioxidant activity and anti-wrinkle effects of Aceriphyllum rossii leaf ethanol extract (ARLEE) in vitro using human dermal fibroblasts. The total polyphenol and flavonoid contents of ARLEE were 578.6 and 206.3 mg/g, respectively. At a concentration of $250{\mu}g/mL$, the electron-donating ability of ARLEE was 87.1%. In comparison with the vehicle, ARLEE treatment at $100{\mu}g/mL$ significantly increased type I procollagen synthesis (p < 0.01) by 50.7%. In vitro ARLEE treatment (10 mg/mL) inhibited collagenase and elastase activity by 97.1% and 99.2%, respectively. Compared with the control, ascorbic acid treatment at $100{\mu}g/mL$ significantly decreased matrix metalloproteinase (MMP)-1 protein expression (p < 0.01) by 37.0%. ARLEE treatment at $50{\mu}g/mL$ significantly decreased MMP-1 protein expression (p < 0.01) by 46.1%. Ascorbic acid and ARLEE treatments at $100{\mu}g/mL$ significantly decreased MMP-1 mRNA expression (p < 0.01) by 26.1% and 36.1%, respectively. From these results, we conclude that ARLEE has excellent antioxidant activity and even better anti-wrinkle effects than ascorbic acid in human dermal fibroblasts. These results suggest that ARLEE could be used in functional cosmetics for the prevention or alleviation of skin wrinkles induced by ultraviolet rays.

Down-modulation of Bis reduces the invasive ability of glioma cells induced by TPA, through NF-κB mediated activation of MMP-9

  • Lee, Young Dae;Cui, Mei Nu;Yoon, Hye Hyeon;Kim, Hye Yun;Oh, Il-Hoan;Lee, Jeong-Hwa
    • BMB Reports
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    • 제47권5호
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    • pp.262-267
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    • 2014
  • Bcl-2 interacting cell death suppressor (Bis) has been shown to have anti-apoptotic and anti-stress functions. Recently, increased Bis expression was reported to correlate with glioma aggressiveness. Here, we investigated the effect of Bis knockdown on the acquisition of the invasive phenotype of A172 glioma cells, induced by 12-O-Tetradecanoylphorbol-3-acetate (TPA), using a Transwell assay. Bis knockdown resulted in a significant decrease in the migration and invasion of A172 cells. Furthermore, Bis knockdown notably decreased TPA-induced matrix metalloproteinase-9 (MMP-9) activity and mRNA expression, as measured by zymography and quantitative real time PCR, respectively. A luciferase reporter assay indicated that Bis suppression significantly down-regulated NF-${\kappa}B$-driven transcription. Finally, we demonstrated that the rapid phosphorylation and subsequent degradation of $I{\kappa}B-{\alpha}$ induced by TPA was remarkably delayed by Bis knockdown. These results suggest that Bis regulates the invasive ability of glioma cells elicited by TPA, by modulating NF-${\kappa}B$ activation, and subsequent induction of MMP-9 mRNA.

Neurotrophic Artemin Promotes Motility and Invasiveness of MIA PaCa-2 Pancreatic Cancer Cells

  • Meng, Ling-Xin;Chi, Yu-Hua;Wang, Xiang-Xu;Ding, Zhao-Jun;Fei, Li-Cong;Zhang, Hong;Mou, Ling;Cui, Wen;Xue, Ying-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권5호
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    • pp.1793-1797
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    • 2012
  • Objective: To analyze the capacity of neurotrophic artemin to promote the motility and invasiveness of MIA PaCa-2 pancreatic cancer cells. Methods: MIA PaCa-2 was cultured in vitro and studied using transwell chambers for motility and invasiveness on treatment with different concentrations of aArtemin or its receptor $GFR{\alpha}3$ were also determined. Expression of matrix metalloproteinase-2 (MMP-2) and epithelial cadherin (E-cadherin) was quantified using RT-PCR and Western blotting. Results: MIA PaCa-2 pancreatic cancer cell motility and invasiveness was significantly increased with artemin and its receptor $GFR{\alpha}3$ with dose dependence (P<0.01). MMP-2 production was also significantly increased (t = 6.35, t = 7.32), while E-cadherin was significantly lowered (t = 4.27, t = 5.61) (P <0.01). Conclusion: Artemin and its receptor $GFR{\alpha}3$ can promote pancreatic cancer cell motility and invasiveness and contribute to aggressive behavior. The mechanism may be related to increased expression of MMP-2 molecule and down-regulation of E-cadherin expression.

수치에 의한 권백의 항산화 효과와 MMP 발현 저해 효과 (Effect of the Processed Selaginella tamariscina on Antioxidation and Inhibition of Matrix Metalloproteinase)

  • 이범천;심관섭;김진희;김진화;표형배
    • 대한화장품학회지
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    • 제32권2호
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    • pp.69-74
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    • 2006
  • 권백은 동양에서 암환자 치료를 위한 전통 약용식물로 알려져 있다. 본 연구에서는 포제기술을 이용한 권백을 항노화 화장품 소재로 적용하고자 다양한 생물학적활성을 평가하였다. 열과 모래를 이용한 포제 권백은 기존 권백을 다른 목적으로 이용하고자 비교하였다. 포제 권백은 페놀함량이 증가하였고 DPPH 라디칼 소거활성도 증가하였다. 세포내 활성산소 소거평가를 위해 사람 섬유아세포를 배양하여 UVB($20 mJ/cm^2$)에 의해 증가된 세포내 활성산소가 포제 권백을 처리함으로써 활성 산소 소거효과가 증가하였다. 사람 섬유아세포에서 UVA에 의해 발현되는 MMP-1효소는 포제 권백에 의해 농도 의존적으로 감소하였다. 결론적으로 포제 권백은 페놀함량의 증가와 항산화 효과가 증가하였고, 자외선에 의한 세포손상을 보호하여 항노화 화장품의 새로운 소재로 이용될 것으로 사료된다.

석화채(石花菜) 추출물 도포가 마우스의 심재성 2도 화상에 미치는 영향 (Effects of Skin Application of Gelidium amansii Extract on Deep Second-degree Burns in Mice)

  • 김동현;홍승욱
    • 대한한의학회지
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    • 제31권2호
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    • pp.36-47
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    • 2010
  • Objective: The purpose of this study was to investigate the effects of skin application with Gelidium amansii extract on skin with deep second degree burns in mice. Methods: BALB/c mice were divided into four groups: normal (NOR) group; burn-elicited mice (CON) group, Silmazine-treated mice after burn elicitation (ST) group, and Gelidium amansii-extract treated mice after burn elicitation (GT) group. To examine the skin recovery effect after burn, changes of burn area, angiogenesis and histologic structure were analyzed. To measure effect of edema regulation, matrix metalloproteinase-9 (MMP-9) was analyzed. To estimate the skin regenerative & stable effect, 5-bromo-2'-deoxyuridine (BrdU) and substance P were analyzed. Results: 2 weeks later, 1. The size of burn area decreased in the GT and ST groups more than the CON group. 2. Alleviation of angiogenesis appeared in the GT and ST groups more than in the CON group. 3. Blood clot, epithelial cell hyperplasia, and inflammatory cell infiltration declined in the GT and ST groups more than in the CON group. 4. MMP-9, BrdU, and substance P positive reaction decreased in the GT and ST groups more than in the CON group 5. In the comparative study, the GT group was superior to the ST group. Conclusion: The skin application of Gelidium amansii extract could lessen skin damage by the medium of regulation MMP-9 activation. This skin stabilization was induced in mice with deep second degree burns.

발효홍삼 추출물의 광노화 피부 보호 효과 (Protective Effect of Fermented Red Ginseng Extracts on Photoaging Skin of Induced by UVB in Hairless Mice)

  • 김호일;오미진;김종석;이성철;권진;이창현
    • 동의생리병리학회지
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    • 제29권1호
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    • pp.58-65
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    • 2015
  • This study is designed to investigate the protective effects of fermented Red Ginseng (FRG) against photoaging in vitro and in vivo. UVB was irradiated to the human keratinocyte HaCaT cell and dorsal skin of SKH-1 mice for the induction of photoaging. After treatment of non-fermented red ginseng (NRG), fermented red ginseng (FRG), and fortified fermented red ginseng (FFRG) to the UVB irradiated HaCaT cell, ROS production and activity of MMP-9 were examined by DCFC-DA assay and gelatin zymographic assay respectively. UVB irradiated SKH-1 mice were treated with NRG, FRG, and FFRG via oral(300 mg/Kg B.W./day) and topical($100{\mu}{\ell}/mouse/day$) route.All of NRG, FRG, and FFRG had significantly reduced the intracellular ROS production elicited by UVB, among them FRG slightly more reduced the ROS production than NRG and FFRG. FFRG had slightly more reduced the MMP-9 activity in UVB irradiated HaCaT cells than NRG and FFRG in high dose. Oral and topical treatment of NRG, FRG, and FFRG had decreased the expression of matrix metalloproteinase-2, -3, and -9 in dorsal skin of UVB irradiated mice. Among them, inhibitory effect of FRG on the expression of MMP-2 was apparent. We speculate that FRG has therapeutic potentials on the UVB irradiated photoaging.

감 추출물의 항산화, 항노화 및 미백 기능 규명 (Identification of Anti-oxidant, Anti-aging, and Whitening Effects of Diospyros kaki Extracts)

  • 홍창의;유수연
    • 대한화장품학회지
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    • 제48권3호
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    • pp.275-285
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    • 2022
  • 본 연구에서는 감(Diospyros kaki)의 1,3-butylene glycol 추출물(DBG)과 에탄올 추출물(DET)를 이용하여 항산화, 항노화 및 미백 기능을 규명하였다. 항산화능은 DPPH와 superoxide dismutase (SOD) assay를 통해 규명하였으며, 그 결과 DBG와 DET 모두 현저한 DPPH 소거능 및 SOD-유사능을 보여주었다. 또한 elastase와 hyaluronidase 억제능 그리고 matrix metalloproteinase (MMP-1) 발현을 통해 항노화 기능을 규명하였다. DBG와 DET 모두 농도의존적으로 elastase와 hyaluronidase를 억제하였으며, MMP-1 발현 역시 저해하였다. 마지막으로 미백 기능을 규명하기 위하여 tyronisinase 억제 및 melanin 생성 저해능을 알아보았는데, DBG 추출물만이 tyrosinase를 저해할 수 있었다. 요약하면, 감 추출물은 강한 항산화, 항노화, 미백 기능을 갖고 있으며, 추후 화장품 소재로 활용이 가능할 것으로 사료된다.