Short exposure to paclitaxel induces multipolar spindle formation and aneuploidy through promotion of acentrosomal pole assembly

Sci China Life Sci. 2010 Nov;53(11):1322-9. doi: 10.1007/s11427-010-4086-1. Epub 2010 Nov 3.

Abstract

Paclitaxel is a widely used microtubule drug and cancer medicine. Here we report that by short exposure to paclitaxel at a low dose, multipolar spindles were induced in mitotic cells without centrosome amplification. Both TPX2 depletion and Aurora-A overexpression antagonized the multipolarity. Live cell imaging showed that some paclitaxel-treated cells accomplished multipolar cell division and a portion of the daughter cells went on to the next round of mitosis. The surviving cells grew into clones with varied genome content. The results indicated that an aneuploidy population could be induced by short exposure to paclitaxel at a low dose, implicating potential side effects of paclitaxel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy*
  • Animals
  • Aurora Kinase A
  • Aurora Kinases
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Centrosome / drug effects*
  • HeLa Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Mitosis / drug effects*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Paclitaxel / pharmacology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Spindle Apparatus / drug effects*
  • Tubulin Modulators / pharmacology*

Substances

  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • TPX2 protein, human
  • Tubulin Modulators
  • Aurka protein, mouse
  • Aurora Kinase A
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Paclitaxel