Apoptosis

, Volume 5, Issue 4, pp 335–343 | Cite as

Bcl-2 protects neuronal cells against taxol-induced apoptosis by inducing multi-nucleation

  • R. Nuydens
  • G. Dispersyn
  • G. Van Den Kieboom
  • M. de Jong
  • R. Connors
  • F. Ramaekers
  • M. Borgers
  • H. Geerts

Abstract

Taxol-induced peripheral neuropathy is a commonly-occurring side-effect in the treatment of cancer patients with taxoteres or taxanes. Taxol is known to induce apoptosis in a number of tumor cells. This report documents that, similar to proliferating cells, taxol induces apoptosis in NGF-differentiated PC12 cells, as assessed by exogenous FITC-annexin-V binding and nuclear fragmentation. It is shown that PC12 cells that stably overexpress Bcl-2 are protected against the toxic effect of taxol, as evidenced by the XTT assay and by a decreased fraction of propididum iodide positive cells in a dye exclusion test. Also the number of annexin-V-positive cells and the number of fragmented nuclei are lower in the Bcl-2 transfected cells. The effect is similar to the protective effect of Bcl-2 against NGF deprivation in differentiated PC12 cells. Although taxol forced both wild-type and Bcl-2-overexpressing cells into a mitotic state, only in Bcl-2-overexpressing cells did this lead to the appearance of metabolically active, multi-nucleated cells. This suggests that Bcl-2 is able to induce an alternative escape pathway, downstream of the G2/M block, in taxol-treated differentiated PC12 cells.

Apoptosis Bcl-2 mitosis PC12 taxol 

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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • R. Nuydens
    • 1
    • 2
  • G. Dispersyn
    • 3
  • G. Van Den Kieboom
    • 1
  • M. de Jong
    • 1
  • R. Connors
    • 4
  • F. Ramaekers
    • 2
  • M. Borgers
    • 1
  • H. Geerts
    • 1
  1. 1.Department of NeurobiologyJanssen Research FoundationBeerseBelgium;
  2. 2.Department of Molecular Cell Biology and GeneticsMaastricht UniversityMaastrichtThe Netherlands
  3. 3.Department of BiochemistryUniversity of AntwerpAntwerpBelgium
  4. 4.Oncology GroupJanssen Research FoundationSpring HouseUSA

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