Length of mitotic arrest induced by microtubule-stabilizing drugs determines cell death after mitotic exit

Cell death induced by agents that disrupt microtubules can kill cells by inducing a prolonged mitotic block. This mitotic block is dependent on the spindle assembly checkpoint, a surveillance system that ensures the bipolar attachment of chromosomes to the mitotic spindle before the onset of anaphas...

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Bibliographic Details
Published in:Molecular cancer therapeutics 2009-06, Vol.8 (6), p.1646-1654
Main Authors: Bekier, Michael E, Fischbach, Robert, Lee, Jennifer, Taylor, William R
Format: Article
Language:English
Subjects:
apoptosis
Aurora kinase
Benzamides - pharmacology
Caspase 3 - metabolism
Cell Death - drug effects
Cell Proliferation - drug effects
Cell Survival - drug effects
Cyclin B - metabolism
Cyclin B1
epothilone B
Epothilones - pharmacology
Fluorescent Antibody Technique
G1 Phase
HeLa Cells
Humans
Mitosis - drug effects
Nocodazole - pharmacology
Paclitaxel - pharmacology
Quinazolines - pharmacology
Taxol
Time Factors
TNF-Related Apoptosis-Inducing Ligand - pharmacology
TRAIL
Tubulin Modulators - pharmacology
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Summary:Cell death induced by agents that disrupt microtubules can kill cells by inducing a prolonged mitotic block. This mitotic block is dependent on the spindle assembly checkpoint, a surveillance system that ensures the bipolar attachment of chromosomes to the mitotic spindle before the onset of anaphase. Under some conditions, the spindle assembly checkpoint can become weakened, allowing cells to exit mitosis despite the presence of chromosomes that are not properly attached to the mitotic spindle. Here, we use an Aurora kinase inhibitor to drive mitotic exit and test the effect of mitotic arrest length on death in the subsequent interphase. Cells that are blocked in mitosis for >15 h die shortly after exiting from mitosis, whereas cells that exit after being blocked for
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.MCT-08-1084