Cancer Cells Display Profound Intra- and Interline Variation following Prolonged Exposure to Antimitotic Drugs

Drugs targeting the mitotic spindle are used extensively during chemotherapy, but surprisingly, little is known about how they kill tumor cells. This is largely because many of the population-based approaches are indirect and lead to vague and confusing interpretations. Here, we use a high-throughpu...

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Bibliographic Details
Published in:Cancer cell 2008-08, Vol.14 (2), p.111-122
Main Authors: Gascoigne, Karen E., Taylor, Stephen S.
Format: Article
Language:English
Subjects:
Antimitotic Agents - pharmacology
Caspases - metabolism
Cell Death - drug effects
Cell Line, Tumor
Cell Lineage - drug effects
CELLBIO
CELLCYCLE
Chromosomal Instability - drug effects
Chromosomes, Human - genetics
Humans
Microscopy
Mitosis - drug effects
Models, Biological
Neoplasms - enzymology
Neoplasms - pathology
Spindle Apparatus - drug effects
Spindle Apparatus - metabolism
Time Factors
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Summary:Drugs targeting the mitotic spindle are used extensively during chemotherapy, but surprisingly, little is known about how they kill tumor cells. This is largely because many of the population-based approaches are indirect and lead to vague and confusing interpretations. Here, we use a high-throughput automated time-lapse light microscopy approach to systematically analyze over 10,000 single cells from 15 cell lines in response to three different classes of antimitotic drug. We show that the variation in cell behavior is far greater than previously recognized, with cells within any given line exhibiting multiple fates. We present data supporting a model wherein cell fate is dictated by two competing networks, one involving caspase activation, the other protecting cyclin B1 from degradation.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2008.07.002