Anti-angiogenic action of 5; 5-diphenyl-2-thiohydantoin-N10 (DPTH-N10).

English | 正體中文 | 简体中文 | Items with full text/Total items : 45422/58598 (78%)
Visitors : 2515142 Online Users : 228

RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.

Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer

TMUIR > College of Medicine > Graduate Institute of Medical Sciences > Periodical Article > Item 987654321/3638

Please use this identifier to cite or link to this item: http://libir.tmu.edu.tw/handle/987654321/3638

Title:	Anti-angiogenic action of 5;5-diphenyl-2-thiohydantoin-N10 (DPTH-N10).
Authors:	李文森 Liu Y;Wu J;Ho PY;Chen LC;Chen JT;Liang YC;Cheng CK;Lee WS
Contributors:	醫學科學研究所
Date:	2008
Issue Date:	2009-08-25 09:55:16 (UTC+8)
Abstract:	Previously, we demonstrated that 5,5-diphenyl-2-thiohydantoin (DPTH) exerts an anti-proliferation effect on subcultured human umbilical vein endothelial cells (HUVEC). In the present study, we show that 2(naphthalen-2-ylmethylsulfanyl)-5,5-diphenyl-1,5-dihydro-imidazol-4-one (DPTH-N10), a derivative compound of DPTH, exerts a 5 times stronger inhibition of [3H]thymidine incorporation into HUVEC as compared with DPTH and at very low concentrations (0–20 μM) inhibited DNA synthesis and decreased cell number in cultured HUVEC in a concentration- and time-dependent manner, but not in human fibroblasts. [3H]thymidine incorporation analysis demonstrated that treatment of HUVEC with DPTH-N10 arrested the cell at the G0/G1 phase of the cell cycle. Western blot analysis revealed that the protein level of p21 in HUVEC increased after DPTH-N10 treatment. In contrast, the protein levels of p27, p53, cyclins A, D1, D3 and E, cyclin-dependent kinase (CDK)2, and CDK4 in HUVEC were not changed significantly after DPTH-N10 treatment. Immunoprecipitation showed that the formation of the CDK2–p21 complex, but not the CDK2–p27, CDK4–p21, and CDK4–p27 complex, was increased in the DPTH-N10-treated HUVEC. Kinase assay further demonstrated that CDK2, but not CDK4, kinase activity was decreased in the DPTH-N10-treated HUVEC. Pretreatment of HUVEC with a p21, but not p27, antisense oligonucleotide reversed the DPTH-N10-induced inhibition of [3H]thymidine incorporation into HUVEC. Taken together, these data suggest that DPTH-N10 inhibits HUVEC proliferation by increasing the level of p21 protein, which in turn inhibits CDK2 kinase activity, and finally interrupts the cell cycle. Capillary-like tube formation, aortic ring culture, and chick embryo chorioallantoic membrane (CAM) assays further demonstrated the anti-angiogenic effect of DPTH-N10. Keywords: Angiogenesis; p21; Proliferation; Endothelial cells; Cyclin-dependent kinase Abbreviations: DPTH-N10, 5,5-diphenyl-2-thiohydantoin-N10; DPT, 5,5-diphenylhydantoin; HUVEC, human umbilical vein endothelial cells; CDK, cyclin-dependent kinase; CAM, chick embryo chorioallantoic membrane; SDS, sodium dodecyl sulfate; ECGS, endothelial cell growth supplement; M199, medium 199; FBS, fetal bovine serum; CKI, CDK-inhibitory protein; FACS, fluorescence-activated cell sorter
Relation:	Cancer Letters.(271):294-305.
Data Type:	article
Appears in Collections:	[Graduate Institute of Medical Sciences] Periodical Article

Files in This Item:

File	Description	Size	Format
55.pdf		598Kb	Adobe PDF	130	View/Open
全文.txt		0Kb	Text	405	View/Open

著作權聲明 Copyright Notice

本平台之數位內容為臺北醫學大學所收錄之機構典藏，包含體系內各式學術著作及學術產出。秉持開放取用的精神，提供使用者進行資料檢索、下載與取用，惟仍請適度、合理地於合法範圍內使用本平台之內容，以尊重著作權人之權益。商業上之利用，請先取得著作權人之授權。
The digital content on this platform is part of the Taipei Medical University Institutional Repository, featuring various academic works and outputs from the institution. It offers free access to academic research and public education for non-commercial use. Please use the content appropriately and within legal boundaries to respect copyright owners' rights. For commercial use, please obtain prior authorization from the copyright owner.
瀏覽或使用本平台，視同使用者已完全接受並瞭解聲明中所有規範、中華民國相關法規、一切國際網路規定及使用慣例，並不得為任何不法目的使用TMUIR。
By utilising the platform, users are deemed to have fully accepted and understood all the regulations set out in the statement, relevant laws of the Republic of China, all international internet regulations, and usage conventions. Furthermore, users must not use TMUIR for any illegal purposes.
本平台盡力防止侵害著作權人之權益。若發現本平台之數位內容有侵害著作權人權益情事者，煩請權利人通知本平台維護人員([email protected])，將立即採取移除該數位著作等補救措施。
TMUIR is made to protect the interests of copyright owners. If you believe that any material on the website infringes copyright, please contact our staff([email protected]). We will remove the work from the repository.

Loading...