Visualization of Aberrant Perinuclear Microtubule Aster Organization by Microtubule-Destabilizing Agents

To analyze aberrant spindle formation by microtubule-targeting drugs, live cell imaging was performed using multi-fluorescent human MDA-MB-435 cells in which several spindle components were visualized. Time-lapse images revealed that nocodazole and vinblastine induced additional perinuclear asters at the onset of mitosis. These results imply that these drugs stimulate the microtubule-organizing activity, despite their microtubule-destabilizing properties.

[1]  N. Rusan,et al.  Reorganization of the microtubule array in prophase/prometaphase requires cytoplasmic dynein-dependent microtubule transport , 2002, The Journal of cell biology.

[2]  Howard J. Worman,et al.  Nuclear Membrane Dynamics and Reassembly in Living Cells: Targeting of an Inner Nuclear Membrane Protein in Interphase and Mitosis , 1997, The Journal of cell biology.

[3]  K. Sugimoto,et al.  Molecular dynamics of Aurora-A kinase in living mitotic cells simultaneously visualized with histone H3 and nuclear membrane protein importinalpha. , 2002, Cell structure and function.

[4]  K. Sugimoto,et al.  Construction of three quadruple-fluorescent MDA435 cell lines that enable monitoring of the whole chromosome segregation process in the living state. , 2008, Mutation research.

[5]  W. B. Derry,et al.  Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. , 1996, Cancer research.

[6]  Kenji Sugimoto,et al.  Differential responses of mitotic spindle pole formation to microtubule-stabilizing agents epothilones A and B at low concentrations , 2008, Cell cycle.

[7]  Y. Hiraoka,et al.  Dynamics of chromosomes and microtubules visualized by multiple‐wavelength fluorescence imaging in living mammalian cells: effects of mitotic inhibitors on cell cycle progression , 1997, Genes to cells : devoted to molecular & cellular mechanisms.

[8]  M. Jordan,et al.  Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. , 1992, Journal of cell science.

[9]  M. Jordan,et al.  Microtubules as a target for anticancer drugs , 2004, Nature Reviews Cancer.

[10]  Live imaging of spindle pole disorganization in docetaxel-treated multicolor cells. , 2007, Biochemical and biophysical research communications.

[11]  M. Jordan,et al.  Mechanism of inhibition of cell proliferation by Vinca alkaloids. , 1991, Cancer research.