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Please use this identifier to cite or link to this item: http://dspace.library.iitb.ac.in/jspui/handle/10054/3725

Title: Antimitotic sulfonamides inhibit microtubule assembly dynamics and cancer cell proliferation
Authors: MOHAN, R
BANERJEE, M
RAY, A
MANNA, T
WILSON, L
OWA, T
BHATTACHARYYA, B
PANDA, D
Keywords: cycle progression
colchicine site
g1 phase
kinetic stabilization
protease inhibitors
in-vitro
anticancer
tubulin
binding
phosphorylation
Issue Date: 2006
Publisher: AMER CHEMICAL SOC
Citation: BIOCHEMISTRY, 45(17), 5440-5449
Abstract: Several sulfonamides have antitumor activities and are currently undergoing clinical evaluation for the treatment of cancer. In this study, we have elucidated the antiproliferative mechanism of action of five indole sulfonamides. The indole sulfonamides inhibited the polymerization of microtubule protein into microtubules in vitro. In addition, three representative derivatives, ER-68378 (2), ER-68384 (4) and ER-68394 (5), suppressed the dynamic instability behavior at the plus ends of individual steady-state microtubules in vitro. The analogues inhibited HeLa cell proliferation with half-maximal inhibitory concentrations in the range of 6-17 mu M. The compounds blocked cell cycle progression at mitosis. At their lowest effective antimitotic concentrations, they depolymerized the spindle microtubules and disorganized the chromosomes but did not affect the microtubules in interphase cells. However, at relatively high concentrations, interphase microtubules were also depolymerized by these sulfonamides. Furthermore, all five compounds were found to induce apoptosis in the cells in association with the phosphorylation of bcl-2. The results suggest that the indole sulfonamides inhibit cell proliferation at mitosis by perturbing the assembly dynamics of spindle microtubules and that they can kill cancer cells by inducing apoptosis through the bcl-2-dependent pathway.
URI: http://dx.doi.org/10.1021/bi0523409
http://dspace.library.iitb.ac.in/xmlui/handle/10054/3725
http://hdl.handle.net/10054/3725
ISSN: 0006-2960
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