Liou JP |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=3.956 ------>paper_class3=2 ------>paper_class2=1 ------>vol=323 ------>confirm_bywho=amel ------>insert_bywho=jpl ------>Jurnal_Rank=17.6 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=405 ------>medlineContent= ------>unit=G0100 ------>insert_date=20071114 ------>iam=1 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=333 ------>journal_name=J. Pharmacol. Exp. Ther. ------>paper_name=A novel oral indoline-sulfonamide agent, J30, exhibits potent activity against human cancer cells in vitro and in vivo through the disruption of microtubule. ------>confirm_date=20071115 ------>tch_id=093131 ------>pmid=17660383 ------>page1=398 ------>fullAbstract=We have previously synthesized a series of 7-aroylaminoindoline-1-sulfonamides as a novel class of antitubulin agents. Here we show that one of these new compounds, N-[1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-7-yl]-isonicotinamide (J30), is potently effective against various resistant and nonresistant cancer cell lines despite the status of multidrug resistance, multidrug-resistance associated protein, or other resistance factors in vitro. J30 inhibits assembly of purified tubulin by strongly binding to the colchicine-binding site. Western blot and immunofluorescence experiments demonstrate that J30 depolymerizes microtubules in the KB cell line, resulting in an accumulation of G2/M phase cells. Further studies indicate that J30 causes cell cycle arrest, as assessed by flow analyses and the appearance of MPM-2 (a specific mitotic marker), and is associated with up-regulation of cyclin B1, phosphorylation of Cdc25C, and dephosphorylation of Cdc2. J30 also causes Bcl-2 phosphorylation, cytochrome c translocation, and activation of the caspase-9 and caspase-3 cascades. These findings suggest that the J30-mediated apoptotic signaling pathway depends on caspases and mitochondria. Finally, we show that oral administration of J30 significantly inhibits tumor growth in NOD/scid mice bearing human oral, gastric, and drug-resistant xenografts. Together, our results suggest that J30 has potential as a chemotherapeutic agent for treatment of various malignancies. ------>tmu_sno=None ------>sno=16170 ------>authors2=Hsu KS ------>authors3=Kuo CC ------>authors4=Chang CY ------>authors5=Chang JY ------>authors6= ------>authors6_c= ------>authors=Liou JP ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=A novel oral indoline-sulfonamide agent, N-[1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-7-yl]-isonicotinamide (J30), exhibits potent activity against human cancer cells in vitro and in vivo through the disruption of microtubule. ------>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=1 |