| Shyu KG |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=1.123 ------>paper_class3=2 ------>paper_class2=1 ------>vol=28 ------>confirm_bywho=None ------>insert_bywho=shyukg ------>Jurnal_Rank=41.6 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=566 ------>medlineContent= ------>unit=000 ------>insert_date=20070412 ------>iam=1 ------>update_date=None ------>author=??? ------>change_event=1 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=Acta Pharmacol Sin ------>paper_name=Antitumor activity of a novel bis-aziridinylnaphthoquinone (AZ4) mediating cell cycle arrest and apoptosis in non-small cell lung cancer cell line NCI-H460 ------>confirm_date=None ------>tch_id=092067 ------>pmid=17376296 ------>page1=559 ------>fullAbstract=AIM: The cytotoxic activities of a series of bis-aziridinylnaphthoquinone, AZ1 to AZ4, on human lung carcinoma cell lines, H460, and normal lung cells fibroblast cell line, MRC-5, and the mechanisms of H460 cells induced by AZ4 were investigated. METHODS: The MTT assay was used to determine the cell proliferation. Cell cycle was analysed by FACS. The activity of caspase 3, 8 and 9 was determined by cell-permeable fluorogenic detection system. Western blot assay was used to evaluate the regulation of cyclin B, Cdc-2, p53, p21, and the Bcl-2 protein. RESULTS: AZ1 to AZ4 displayed various cytotoxicity activities against H460 and MRC-5 cells. Compared to those compounds, AZ4 was with the most effective agent among the 5 tested analogues at reducing H460 cell viability with an IC(50) value of 1.23 micromol/L; it also exhibited weak cytotoxicity against MRC-5 cells with an IC(50) value of 12.7 micromol/L. The results show that growth arrest on the G2-M phase of H460 cells induced by AZ4 for 24 h was discovered, and this might be altered with the reduced Cdc-2 protein expression of 47% at 2.0 micromol/L AZ4, but not with cyclin B protein expression. The AZ4 treated cells were then led to apoptosis after 48 h. This was associated with the activation of apoptotic enzyme caspase 3 and mediated by caspase 8, but not caspase 9 at various concentrations of AZ4 after being cultured for 48 h and 30 h, respectively. The anti-apoptotic protein (Bcl-2) expression in H460 cells altered by 39% with downregulation, and the p53 protein by 25% with upregulation after being cultured with 2.0 micromol/L AZ4 for 48 h. In a time-dependent manner, the expression of the p53 and p21 proteins were increased to the maximum at 24 h, and then decreased at 48. CONCLUSION: AZ4 represents a novel antitumor aziridinylnaphthoquinone with therapeutic potential against the non-small cell lung cancer cells. ------>tmu_sno=None ------>sno=14887 ------>authors2=Huang ST ------>authors3=Kuo HS ------>authors4=Cheng WP ------>authors5=Lin YL ------>authors6= ------>authors6_c= ------>authors=Shyu KG ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Antitumor activity of a novel bis-aziridinylnaphthoquinone (AZ4) mediating cell cycle arrest and apoptosis in non-small cell lung cancer cell line NCI-H460. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2007 ------>submit_flag=None ------>publish_month=4 |