Record Details

Curcumin suppresses the dynamic instability of microtubules, activates the mitotic checkpoint and induces apoptosis in MCF-7 cells

DSpace at IIT Bombay

View Archive Info
 
 
Field Value
 
Title Curcumin suppresses the dynamic instability of microtubules, activates the mitotic checkpoint and induces apoptosis in MCF-7 cells
 
Creator BANERJEE, M
SINGH, P
PANDA, D
 
Subject spindle assembly checkpoint
breast-cancer cells
tubulin binding
individual microtubules
kinetic stabilization
cycle arrest
inhibition
p53
induction
polymerization
apoptosis
bubr1
combination study
delayed mitosis
dynamic instability
 
Description In this study, curcumin, a potential anticancer agent, was found to dampen the dynamic instability of individual microtubules in living MCF-7 cells. It strongly reduced the rate and extent of shortening states, and modestly reduced the rate and extent of growing states. In addition, curcumin decreased the fraction of time microtubules spent in the growing state and strongly increased the time microtubules spent in the pause state. Brief treatment with curcumin depolymerized mitotic microtubules, perturbed microtubule-kinetochore attachment and disturbed the mitotic spindle structure. Curcumin also perturbed the localization of the kinesin protein Eg5 and induced monopolar spindle formation. Further, curcumin increased the accumulation of Mad2 and BubR1 at the kinetochores, indicating that it activated the mitotic checkpoint. In addition, curcumin treatment increased the metaphase/anaphase ratio, indicating that it can delay mitotic progression from the metaphase to anaphase. We provide evidence suggesting that the affected cells underwent apoptosis via the p53-dependent apoptotic pathway. The results support the idea that kinetic stabilization of microtubule dynamics assists in the nuclear translocation of p53. Curcumin exerted additive effects when combined with vinblastine, a microtubule depolymerizing drug, whereas the combination of curcumin with paclitaxel, a microtubule-stabilizing drug, produced an antagonistic effect on the inhibition of MCF-7 cell proliferation. The results together suggested that curcumin inhibited MCF-7 cell proliferation by inhibiting the assembly dynamics of microtubules.
 
Publisher WILEY-BLACKWELL PUBLISHING, INC
 
Date 2011-09-01T11:38:35Z
2011-12-26T12:59:38Z
2011-12-27T05:52:10Z
2011-09-01T11:38:35Z
2011-12-26T12:59:38Z
2011-12-27T05:52:10Z
2010
 
Type Article
 
Identifier FEBS JOURNAL, 277(16), 3437-3448
1742-464X
http://dx.doi.org/10.1111/j.1742-4658.2010.07750.x
http://dspace.library.iitb.ac.in/xmlui/handle/10054/12768
http://hdl.handle.net/10054/12768
 
Language en