Bcl-2 protects neuronal cells against taxol-induced apoptosis by inducing multi-nucleation
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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.
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- Bcl-2 protects neuronal cells against taxol-induced apoptosis by inducing multi-nucleation
Volume 5, Issue 4 , pp 335-343
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- Kluwer Academic Publishers
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- 1. Department of Neurobiology, Janssen Research Foundation, Beerse, Belgium;
- 2. Department of Molecular Cell Biology and Genetics, Maastricht University, Maastricht, The Netherlands
- 3. Department of Biochemistry, University of Antwerp, Antwerp, Belgium
- 4. Oncology Group, Janssen Research Foundation, Spring House, Pennsylvania, USA