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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/2737
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| Title: | A novel oral indoline-sulfonamide agent, N-[1-(4-Methoxy-benzenesulfonyl)-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 |
| Authors: | Liou, JP;Hsu, KS;Kuo, CC;Chang, CY;Chang, JY |
| Contributors: | National Institute of Cancer Research |
| Abstract: | We have previously synthesized a series of 7-aroylaminoindoline1- -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 G(2)/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. |
| Keywords: | Pharmacology & Pharmacy |
| Date: | 2007-10 |
| Relation: | Journal of Pharmacology and Experimental Therapeutics. 2007 Oct;323(1):398-405. |
| Link to: | http://dx.doi.org/10.1124/jpet.107.126680 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-3565&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000249588900045 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34548857118 |
| Appears in Collections: | [張俊彥] 期刊論文
[郭靜娟] 期刊論文
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| 000249588900045.pdf | | 393Kb | Adobe PDF | 544 | View/Open |
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