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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/22285

    標題: A novel polyacetylene significantly inhibits angiogenesis and promotes apoptosis in human endothelial cells through activation of the CDK inhibitors and caspase-7
    作者: WU Li-Wha
    CHIANG Yi-Ming
    CHUANG Hsiao-Ching
    LO Chiu-Ping
    YANG Kai-Ying
    WANG Sheng-Yang
    SHYUR Lie-Fen
    貢獻者: 藥物科技研究所
    關鍵字: Bidens pilosa
    CDK inhibitors
    日期: 2007-06
    上傳時間: 2010-01-15 14:39:43 (UTC+8)
    出版者: Georg Thieme Verlag Kg
    摘要: A novel bioactive polyacetylene compound, 1,2-dihydroxy-5(E)-tridecene-7,9,11-triyne (compound 1), was identified from the Bidens pilosa extract using an ex vivo primary human umbilical vein endothelium cell (HUVEC) bioassay-guided fractionation protocol. Our results demonstrate that compound 1 (at 2.5 microg/mL) possessed significant anti-angiogenic effects, as manifested by an inhibition of HUVEC proliferation, migration, and the formation of tube-like structures in collagen gel. Moreover, compound 1 induced HUVECs to undergo cell death in a concentration- and time-dependent manner. The mechanisms underlying these pharmacological effects include reduced expression of cell cycle mediators such as CDK4, cyclins D1 and A, retinoblastoma (Rb) and vascular endothelial growth factor receptor 1 (VEGFR-1), and promotion of caspase-mediated activation of CDK inhibitors p21(Cip1) and p27(Kip). Moreover, apoptotic induction in HUVECs mediated by compound 1 was found to be in part through overexpression of FasL protein, down-regulation of anti-apoptotic Bcl-2, and activation of caspase-7 and poly(ADP-ribose) polymerase. This study demonstrates the potent anti-angiogenic and apoptotic activities of compound 1, suggesting that phytocompounds such as polyacetylenes deserve more attention regarding their potential as candidates for anti-angiogenic therapeutics.
    關聯: Planta Medica 73(7): p.655-661
    Appears in Collections:[藥學系(所)] 期刊論文

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