English  |  正體中文  |  简体中文  |  Items with full text/Total items : 90120/105277 (86%)
Visitors : 8143807      Online Users : 1617
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version


    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/8369


    Title: EPOX Inhibits Angiogenesis by Degradation of Mcl-1 through ERK Inactivation
    Authors: Sun, Hui-Lung;Tsai, An-Chi;Pan, Shiow-Lin;Ding, Qingqing;Yamaguchi, Hirohito;Lin, Chun-Nan;Hung, Mien-Chie;Teng, Che-Ming
    Contributors: Department of Biotechnology
    Keywords: ENDOTHELIAL-CELLS;DOWN-REGULATION;CANCER-CELLS;XANTHONE DERIVATIVES;BCL-2 PROTEINS;BREAST-CANCER;TUMOR-GROWTH;APOPTOSIS;BAX;EXPRESSION
    Date: 2009-08
    Issue Date: 2010-03-26 10:30:08 (UTC+8)
    Publisher: Asia University
    Abstract: Purpose: Antiangiogenic therapy is considered as an effective strategy for controlling the growth and metastasis of tumors. Among a myriad of biological activities described for xanthone derivatives, the anticancer activity is quite remarkable, but the molecular mechanism is not clearly resolved. In the present study, we investigated the antiangiogenic mechanism of 3,6-di(2,3-epoxypropoxy)xanthone (EPOX), a novel Mcl-1 targeting drug.
    Experimental Design: To evaluate the antiangiogenic activity of EPOX, we did cell viability, cell cycle, tube formation assay in vitro, and Matrigel plug assay in vivo. To evaluate the effect of EPOX on the endothelial signaling pathway, we did immunoblotting, immunoprecipitation, and immunofluorescence analysis. Intracellular glutathione levels were determined with the use of monochlorobimane, a glutathione-specific probe.
    Results: EPOX induced endothelial cell apoptosis in association with proteasome-dependent Mcl-1 degradation. Down-regulation of Mcl-1 resulted in an increase in Mcl-1-free Bim, activation of Bax, and then signaling of mitochondria-mediated apoptosis. Additionally, glutathione depletion and extracellular signal-regulated kinase (ERK) inactivation was observed in EPOX-treated cells. Glutathione supplementation reversed the inhibitory effects of EPOX on ERK, which increases the phosphorylation of Mcl-1 at T-163. Overexpression of mitogen-activated protein/ERK kinase (MEK) partially reversed the effect of EPOX on Mcl-1 dephosphorylation, ubiquitination, and degradation, further implicating ERK in the regulation of Mcl-1 stability.
    Conclusions: This study provides evidence that EPOX induces glutathione depletion, ERK inactivation, and Mcl-1 degradation on endothelial cells, which leads to inhibition of angiogenesis. Our results suggest that EPOX is a novel antiangiogenic agent, making it a promising lead compound for further development in the treatment of angiogenesis-related pathologies.
    Relation: CLINICAL CANCER RESEARCH, 15(15),4904-4914.
    Appears in Collections:[生物科技學系] 期刊論文

    Files in This Item:

    File Description SizeFormat
    269.docx0KbUnknown116View/Open
    269.doc40KbMicrosoft Word503View/Open


    All items in ASIAIR are protected by copyright, with all rights reserved.


    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback