Title

Quantitative Multi-Parametric Evaluation of Centrosome Declustering Drugs: Centrosome Amplification, Mitotic Phenotype, Cell Cycle and Death

Authors

Vaishali Pannu, Georgia State UniversityFollow
Ritu Aneja, Georgia State UniversityFollow
Angela Ogden, Georgia State UniversityFollow
A. Cheng, Georgia State University
PCG Rida, Georgia State University
R. Osan, Georgia State University
Robert Clewley, Georgia State UniversityFollow

Document Type

Article

Publication Date

2014

Abstract

Unlike normal cells, cancer cells contain amplified centrosomes and rely on centrosome clustering mechanisms to form a pseudobipolar spindle that circumvents potentially fatal spindle multipolarity (MP). Centrosome clustering also promotes lowgrade chromosome missegregation, which can drive malignant transformation and tumor progression. Putative ‘centrosome declustering drugs’ represent a cancer cell-specific class of chemotherapeutics that produces a common phenotype of centrosome declustering and spindle MP. However, differences between individual agents in terms of efficacy and phenotypic nuances remain unexplored. Herein, we have developed a conceptual framework for the quantitative evaluation of centrosome declustering drugs by investigating their impact on centrosomes, clustering, spindle polarity, cell cycle arrest, and death in various cancer cell lines at multiple drug concentrations over time. Surprisingly, all centrosome declustering drugs evaluated in our study were also centrosome-amplifying drugs to varying extents. Notably, all declustering drugs induced spindle MP, and the peak extent of MP positively correlated with the induction of hypodiploid DNA-containing cells. Our data suggest acentriolar spindle pole amplification as a hitherto undescribed activity of some declustering drugs, resulting in spindle MP in cells that may not have amplified centrosomes. In general, declustering drugs were more toxic to cancer cell lines than non-transformed ones, with some exceptions. Through a comprehensive description and quantitative analysis of numerous phenotypes induced by declustering drugs, we propose a novel framework for the assessme

Comments

Originally Posted in:

Cell Death and Disease (2014) 5, e1204, DOI:10.1038/cddis.2014.164

Recommended Citation

Pannu, Vaishali; Aneja, Ritu; Ogden, Angela; Cheng, A.; Rida, PCG; Osan, R.; and Clewley, Robert, "Quantitative Multi-Parametric Evaluation of Centrosome Declustering Drugs: Centrosome Amplification, Mitotic Phenotype, Cell Cycle and Death" (2014). Biology Faculty Publications. 7.
https://scholarworks.gsu.edu/biology_facpub/7

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