The anti-proliferation effect of 2-(Naphthalen-2-ylmethylsulfanyl)-5,5-diphenyl-1,5-dihydro-imidazol-4-one（SDil-N10）in human vascular endothelial cells

• Main Authors: Yuan Liu, 劉媛
• Other Authors: Wen-Sen Lee, Ph.D.
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/27079856038903848465

碩士 === 臺北醫學大學 === 醫學研究所 === 92 === The aim of this study was to examine the anti-proliferation effect of 2-(Naphthalen-2-ylmethylsulfanyl)-5,5-diphenyl-1,5-dihydro- imidazol- 4-one (SDil-N10), an analogue of antiepileptic drug phenytoin(5,5- diphenylhydantoin, DPT), on human umbilical vein endothelial cells (HUVEC) and its possible molecular mechanism underlying. SDil-N10 at a range of concentrations (10-50 uM) dose- and time-dependently inhibited DNA synthesis and decreased cell number in cultured HUVEC, but less effect in human fibroblasts. [3H] Thymidine incorporation assay demonstrated that treatment of HUVEC with SDil-N10 arrested the cell at the G0/G1 phase of the cell cycle. Western blot analysis revealed that the protein levels of p21 and p27 increased and cyclin A decreased after SDil-N10 treatment. In contrast, the protein levels of p53, cyclin D1, D3 and E, cyclin-dependent kinase (CDK2, and CDK4) in HUVEC were not changed significantly after SDil-N10 treatment. Immunoprecipitation showed that the formation of the CDK2-p21 complex, but not the CDK4-p21, CDK2-p27 and CDK4-p27 complex, was increased in the SDil-N10-treated HUVEC. Kinase assay further demonstrated that CDK2, but not CDK4, kinase activity was decreased in the SDil-N10-treated HUVEC. SDil-N10 also inhibited vascular endothelial growth factor (VEGF) induced endothelial cells proliferation. 2D-Matrigel and rat aorta tube formation assays further showed that SDil-N10 inhibited HUVEC tube formation. Taken together, these data suggest that SDil-N10 inhibits HUVEC proliferation by increasing the level of p21 protein, which in turn inhibits CDK2 kinase activity, and finally interrupts the cell cycle. The findings from the present study suggest that SDil-N10 might have the potential to inhibit the occurrence of angiogenesis.