DSpace
 

DSpace at IIT Bombay >
IITB Publications >
Article >

Please use this identifier to cite or link to this item: http://dspace.library.iitb.ac.in/jspui/handle/10054/4642

Title: Brominated derivatives of noscapine are potent microtubule-interfering agents that perturb mitosis and inhibit cell proliferation
Authors: ZHOU, J
GUPTA, K
AGGARWAL, S
ANEJA, R
CHANDRA, R
PANDA, D
JOSHI, HC
Keywords: ovarian-cancer cells
multidrug-resistance
mammalian-cells
gamma-tubulin
dynamics
spindle
pharmacokinetics
polymerization
progression
paclitaxel
Issue Date: 2003
Publisher: AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Citation: MOLECULAR PHARMACOLOGY, 63(4), 799-807
Abstract: 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.
URI: 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
ISSN: 0026-895X
Appears in Collections:Article

Files in This Item:

There are no files associated with this item.

View Statistics

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback