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Brominated derivatives of noscapine are potent microtubule-interfering agents that perturb mitosis and inhibit cell proliferation

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Title Brominated derivatives of noscapine are potent microtubule-interfering agents that perturb mitosis and inhibit cell proliferation
 
Creator ZHOU, J
GUPTA, K
AGGARWAL, S
ANEJA, R
CHANDRA, R
PANDA, D
JOSHI, HC
 
Subject ovarian-cancer cells
multidrug-resistance
mammalian-cells
gamma-tubulin
dynamics
spindle
pharmacokinetics
polymerization
progression
paclitaxel
 
Description Noscapine, a microtubule-interfering agent, has been shown to arrest mitosis, to induce apoptosis, and to have potent antitumor activity. We report herein that two brominated derivatives of noscapine, 5-bromonoscapine (5-Br-nosc) and reduced-5-bromonoscapine (Rd 5-Br-nosc), have higher tubulin binding activity than noscapine and affect tubulin polymerization differently from noscapine. In addition, they are able to arrest cell cycle progression at mitosis at concentrations much lower than noscapine. Interestingly, whereas noscapine-arrested cells have nearly normal bipolar spindles, cells arrested by 5-Br-nosc and Rd 5-Er-nosc form multipolar spindles. Nevertheless, noscapine and the two derivatives all affect the attachment of chromosomes to spindle microtubules and they impair the, tension across paired kinetochores to similar degrees. 5-Br-nose and Rd 5-Br-nosc are also more active than noscapine in inhibiting the proliferation of various human cancer cells, including those that are resistant to paclitaxel and epothilone. Our results thus indicate a great potential for the use of 5-Br-nosc and Rd 5-Br-nosc both as biological tools for studying microtubule-mediated processes and as chemotherapeutic agents for the treatment of human cancers.
 
Publisher AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
 
Date 2011-07-17T06:38:33Z
2011-12-26T12:50:09Z
2011-12-27T05:36:12Z
2011-07-17T06:38:33Z
2011-12-26T12:50:09Z
2011-12-27T05:36:12Z
2003
 
Type Article
 
Identifier MOLECULAR PHARMACOLOGY, 63(4), 799-807
0026-895X
http://dx.doi.org/10.1124/mol.63.4.799
http://dspace.library.iitb.ac.in/xmlui/handle/10054/4642
http://hdl.handle.net/10054/4642
 
Language en