Yu CH |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=67 ------>confirm_bywho=sheujr ------>insert_bywho=wslee ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author=1 ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=1910 ------>medlineContent= ------>unit=E0200 ------>insert_date=20040420 ------>iam=7 ------>update_date=None ------>author=??? ------>change_event=5 ------>ISSN=None ------>authors_c=None ------>score=487 ------>journal_name=Biochemical Pharmacology ------>paper_name=Anti-proliferation effect of 3-amino-2-imino-3,4-dihydro-2H-1,3-benzothiazin-4-one (BJ-601) in human vascular endothelial cells: G0/G1 p21-associated cell cycle arrest. ------>confirm_date=20040506 ------>tch_id=086001 ------>pmid=15130767 ------>page1=1907 ------>fullAbstract=The aim of this study was to examine the anti-proliferation effect of 3-amino-2-imino-3,4-dihydro-2H-1,3-benzothiazin-4-one (BJ-601) on human vascular endothelial cells and its possible molecular mechanism underlying. Our data showed that BJ-601 at a range of concentrations (0-40 microM) dose- and time-dependently decreased cell number in cultured human dermal microvascular endothelial cells (HDMVECs), but not human fibroblasts. The BJ-601-induced growth inhibition in HDMVECs was reversible. [3H]thymidine incorporation demonstrated that BJ-601 arrested the HDMVECs at the G0/G1 phase of the cell cycle. Western blot analysis revealed that BJ-601 (0-40 microM) dose-dependently increased the levels of the protein p21, but not of p27, p53, cyclins A, D1, D3 and E, cyclin-dependent kinase 2 (CDK2), and CDK4 in HDMVECs. Immunoprecipitation showed that the formation of the CDK2-p21 complex, but not CDK2-p27, CDK4-p21 and CDK4-p27 complexes, was increased in the BJ-601-treated HDMVECs. Kinase assay further demonstrated that CDK2, but not CDK4, kinase activity was decreased in a dose-dependent manner in the BJ-601-treated HDMVECs. Pretreatment of HDMVECs with a p21 antisense oligonucleotide, which blocked the expression of p21 protein, reversed the BJ-601-induced inhibition of [3H]thymidine incorporation into HDMVECs. Moreover, cotreatment of the endothelial cells with protein kinase C (PKC) inhibitor, staurosporine, prevented the BJ-601-induced decrease of [3H]thymidine incorporation into HDMVECs. Administration of BJ-601 dose-dependently inhibited capillary-like tube formation of HDMVECs in Matrigel. In conclusion, these data suggest that BJ-601 inhibits HDMVECs proliferation by increasing the level of p21 protein, which in turn inhibits CDK2 kinase activity, and finally causes retardation of the cell cycle at the G0/G1 phase. ------>tmu_sno=None ------>sno=8567 ------>authors2=Wu J ------>authors3=Su YF ------>authors4=Ho PY ------>authors5=Liang YC ------>authors6=Sheu MT, Lee WS ------>authors6_c=None ------>authors=Yu CH ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=Anti-proliferation effect of 3-amino-2-imino-3,4-dihydro-2H-1,3-benzothiazin-4-one (BJ-601) on human vascular endothelial cells: G0/G1 p21-associated cell cycle arrest. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2004 ------>submit_flag=None ------>publish_month=None |