A novel polyacetylene significantly inhibits angiogenesis and promotes apoptosis in human endothelial cells through activation of the CDK inhibitors and caspase-7

doi:10.1055/s-2007-981527

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/22285

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

Title:	A novel polyacetylene significantly inhibits angiogenesis and promotes apoptosis in human endothelial cells through activation of the CDK inhibitors and caspase-7
Authors:	WU Li-Wha CHIANG Yi-Ming CHUANG Hsiao-Ching LO Chiu-Ping YANG Kai-Ying WANG Sheng-Yang SHYUR Lie-Fen
Contributors:	藥物科技研究所
Keywords:	Bidens pilosa Compositae polyacetylenes HUVEC angiogenesis apoptosis CDK inhibitors
Date:	2007-06
Issue Date:	2010-01-15 14:39:43 (UTC+8)
Publisher:	Georg Thieme Verlag Kg
Abstract:	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.
Relation:	Planta Medica 73(7)： p.655-661
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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