| Chang JY |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=3.436 ------>paper_class3=2 ------>paper_class2=1 ------>vol=65 ------>confirm_bywho=None ------>insert_bywho=jpl ------>Jurnal_Rank=20.3 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=2019 ------>medlineContent= ------>unit=000 ------>insert_date=20050404 ------>iam=4 ------>update_date=None ------>author=??? ------>change_event=2 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=Biochemical Pharmacology ------>paper_name=Dual inhibition of topoisomerase I and tubulin polymerization by BPR0Y007, a novel cytotoxic agent. ------>confirm_date=None ------>tch_id=093131 ------>pmid=12787881 ------>page1=2009 ------>fullAbstract=Through the screening of DNA topoisomerase I (Top I) inhibitors, a new cytotoxic agent, BPR0Y007 [2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone], was identified. BPR0Y007 was less potent than camptothecin (CPT) in the inhibition of Top I in vitro. Also, in vitro data showed that BPR0Y007 induces DNA cleavage in the presence of Top I at micromolar concentrations, with a cleavage specificity similar to that of CPT. High concentrations of BPR0Y007 did not produce detectable DNA unwinding, suggesting that BPR0Y007 is not a DNA intercalator. However, BPR0Y007 displaced Hoechst 33342 dye, suggesting that BPR0Y007 binds to DNA at the Hoechst 33342 binding site. Furthermore, BPR0Y007 generated protein-linked DNA breaks in a cell-based study. Cell cycle analysis demonstrated that the cell cycle effect of BPR0Y007 differs from that of CPT. Cells accumulated in the S-phase when treated with high concentrations of CPT, whereas cells accumulated gradually in the G(2)/M phase when treated with increasing concentrations of BPR0Y007. Further studies showed that BPR0Y007 inhibits tubulin polymerization in vivo and in vitro, and induces apoptosis in a concentration-dependent manner. No cross-resistance with BPR0Y007 was observed in CPT-, VP-16-, or vincristine-resistant cell lines. The IC(50) of BPR0Y007 for various human cancer cell lines ranged from 1 to 8 microM. Taken together, these results suggest that BPR0Y007 acts on both Top I and tubulin. Given its unique biochemical mechanisms of action, BPR0Y007 warrants exploration as an antitumor compound. ------>tmu_sno=None ------>sno=10645 ------>authors2=Hsieh HP ------>authors3=Pan WY ------>authors4=Liou JP ------>authors5=Bey SJ ------>authors6=Chen LT, Liu JF,Song JS ------>authors6_c= ------>authors=Chang JY ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Dual inhibition of topoisomerase I and tubulin polymerization by BPR0Y007, a novel cytotoxic agent. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2003 ------>submit_flag=None ------>publish_month=1 |