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/10054/3671

Title: Kinetic stabilization of microtubule dynamics by estramustine is associated with tubulin acetylation, spindle abnormalities, and mitotic arrest
Authors: MOHAN, R
PANDA, D
Keywords: refractory prostate-cancer
phase-ii
in-vivo
antimicrotubule activity
individual microtubules
suppresses dynamics
cell proliferation
kinetochore pairs
assembly invitro
alpha-tubulin
Issue Date: 2008
Publisher: AMER ASSOC CANCER RESEARCH
Citation: CANCER RESEARCH, 68(15), 6181-6189
Abstract: Estramustine (EM) alone or in combination with other anticancer agents is clinically used for the treatment of hormone refractory prostate cancer. Furthermore, EM has been shown to potently inhibit the proliferation of different types of cancer cells in culture apparently by targeting microtubules; however, the antiproliferative mechanism of action of EM is not clear. In this work, we have shown that EM strongly suppressed the dynamic instability of individual microtubules in MCF-7 cells by reducing the rates of growing and shortening excursions and increasing the time microtubule spent in the pause state. At its half maximal proliferation inhibitory concentration (IC50), EM exerted strong suppressive effects on the dynamics of microtubules in MCF-7 cells without detectably affecting either the organization or the polymerized mass of microtubules. At relatively high concentrations (5 X IC50), EM significantly depolymerized microtubules in the cells. Furthermore, the microtubules were found highly acetylated, supporting the conclusion that they were stabilized by the drug. EM treatment induced spindle abnormalities in MCF-7 cells, and a major population of the arrested mitotic cells was multipolar. EM also perturbed the microtubule-kinetochore interaction, thereby activating the spindle assembly checkpoint and leading to apoptotic cell death.
URI: http://dx.doi.org/10.1158/0008-5472.CAN-08-0584
http://dspace.library.iitb.ac.in/xmlui/handle/10054/3671
http://hdl.handle.net/10054/3671
ISSN: 0008-5472
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