The anti-proliferation effect of 5,5-Diphenyl-2-thiohydantoin ( SDil-1 ) in human vascular endothelial cells

• Main Authors: Chun-Ru Shih, 施純如
• Other Authors: Wen-Sen Lee
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/35257283860651709099

碩士 === 台北醫學院 === 醫學研究所 === 90 === The aim of this study is to examine the antiproliferation effect of SDil-1 （5,5-Diphenyl-2-thiohydantoin）in human umbilical vein endothelial cells （HUVEC）and its possible underlying mechanism. Our data demonstrated that SDil-1 caused an inhibition in HUVEC proliferation. The result of 3H-Thymidine incorporation showed that SDil-1 decreased DNA synthesis in HUVEC. Flow cytometric analysis demonstrated that treatment of HUVEC with SDil-1 arrested the cell at the G0/G1 phase of the cell cycle. Western blot analysis showed that treatment of HUVEC with SDil-1 for 21h increased the levels of p21 protein but decreased the level of cdk4, cyclin D3, and cyclin A proteins. The expression of p53、p27, cdk2, cyclinD1 and cyclin E levels did not significantly change as compared with untreated cells. Furthermore, immunoprecipitation study showed that the cdk4-cyclin-linked p21 and the cdk2-cyclin-linked p21 proteins were increased after SDil-1 treatment. Using kinase assay method to measure the kinase activity, we demonstrated that the cdk2 activity was decreased in the SDil-1 treated HUVEC. Thus, our results suggest that SDil-1 can interrupt the cell cycle progression and proliferation of human endothelial cells by inhibiting the cyclin-dependent kinase activity. The findings from the present study suggest that SDil-1 might have the potential to inhibit the occurrence of angiogenesis.