@article {Liou398, author = {Jing-Ping Liou and Kuo-Shun Hsu and Ching-Chuan Kuo and Chi-Yen Chang and Jang-Yang Chang}, title = {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}, volume = {323}, number = {1}, pages = {398--405}, year = {2007}, doi = {10.1124/jpet.107.126680}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/323/1/398}, eprint = {https://jpet.aspetjournals.org/content/323/1/398.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }