Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations.

The results indicate that taxol shares a common antiproliferative mechanism with vinblastine

M. A. Jordan; R. J. Toso; D. Thrower; L. Wilson

2006

Scholarcy highlights

  • Taxol inhibited HeLa cell proliferation by inducing a sustained mitotic block at the metaphase/anaphase boundary
  • We found that low concentrations of vinblastine inhibit dynamic instability and treadmilling of reassembled bovine brain microtubules in vitro without appreciably affecting the microtubule polymer mass
  • We found that low concentrations of taxol inhibited mitosis in HeLa cells and suppressed dynamic instability at the ends of bovine brain microtubules in vitro in the absence of enhanced microtubule polymerization
  • For analysis of the effects of taxol on dynamic instability, microtubules were assembled to steady state by adding bovine brain tubulin in the continuous presence of taxol onto the ends of Strongylocentrotus purpuratus sperm flagella axonemal seeds
  • Very low concentrations of taxol are sufficient to inhibit proliferation of HeLa cells. Both half-maximal inhibition of proliferation and 50% blockage in mitotic metaphase occurred at 8 nM taxol
  • Inhibition was associated with formation of an incomplete metaphase plate of chromosomes and an arrangement of spindle microtubules that strongly resembled the abnormal organization that occurs with low concen
  • Recent evidence indicates that mitotic block induced in HeLa cells by taxol at low concentrations leads to inhibition of cell proliferation and to cell killing

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