Bcl-2 protects neuronal cells against taxol-induced apoptosis by inducing multi-nucleation
Cite this article as: Nuydens, R., Dispersyn, G., Van Den Kieboom, G. et al. Apoptosis (2000) 5: 335. doi:10.1023/A:1009683425260 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 References
Shu C, YangW, Kuo M-L, Huang T-S. Cell cycle G2/M arrest and activation of cyclin-dependent kinases associated with lowdose paclitaxel-induced sub-G1 apoptosis.
Nuydens R, de Jong M, Van Den Kieboom G,
. Okadaic acid-induced apoptosis in neuronal cells: Evidence for a abortive mitotic attempt.
Freeman R, Estus S, Johnson E Jr. Analysis of cell cycle related gene expression in post-mitotic neurons: Selective induction of cyclin D1 during programmed cell death.
Bcl-2 protects neuronal cells from taxol toxicity
Bonfoco E, Ceccatelli S, Manzo L, Nicotera P. Colchicine induces apoptosis in cerebellar granule cells.
Exp Cell Res 1996; 218: 189–200.
Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis.
Tanabe H, Eguchi Y, Kamada S, Martinou JC, Tsujimoto Y. Susceptibility of cerebellar neurons derived from Bcl-2-deficient and transgenic mice to cell death.
Eur J Neurosci
Ottilie S, Diaz JL, Chang J,
. Structural and functional complementation of an inactive Bcl-2 mutant by Bax truncation.
J Biol Chem
Schutte B, Nuydens R, Geerts H, Ramaekers F. Annexin V binding assay as a tool to measure apoptosis in differentiated neuronal cells.
J Neurosci Methods
Park DS, Morris EJ, Stefanis L,
. Multiple pathways of neuronal death induced by DNA-damaging agents, NGF deprivation and oxidative stress.
Bergeron L, Yuan J. Sealing one's fate: Control of cell death in neurons.
Curr Opin Neurobiol
Lam M, Dubyak G, Chen L, Nunez G, Miesfeld R, Distelhorst C. Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca
Proc Natl Acad Sci
Zamzami N, Susin S, Marchetti P,
et al. Mitochondrial control of nuclear apoptosis. J Exp Med 1996; 138: 1533–1544.
Suzuki A, Tsutomi Y. Bcl-2 accelerates the neuronal differentiation: New evidence approaching to the biofunction of Bcl-2 in the neuronal system.
Malgrange B, Delree P, Rigo JM, Baron H, Moonen G. Image analysis of neuritic regeneration by adult dorsal root ganglion neurons in culture: Quantification of the neurotoxicity of anticancer agents and of its prevention by nerve growth factor or basic fibroblast growth factor but not brain-derived neurotrophic factor or neurotrophin-3.
J Neurosci Methods
Furukawa K, Mattson MP. Taxol stabilizes Ca
and protects hippocampal neurons against excitotoxicity.
Burke WJ, Raghu G, Strong R. Taxol protects against calciummediated cell death of differentiated rat pheochromocytoma cells.
Martinou J, Dubois-Dauphin M, Staple J,
. Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia.
Sagot Y, Dubois-Dauphin M, Tan S,
. Bcl-2 overexpression prevents motorneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease.
Haldar S, Basu A, Croce M. Bcl-2 is the guardian of microtubule integrity.
Minn A, Boise L, Thompson C. Expression of Bcl-XL and loss of p53 can cooperate to overcome a cell cycle checkpoint induced by mitotic spindle damage.
Genes & Development 1996: 10: 2621–2631.
Ibrado A, Huang Y, Fang G, Bhalla K. Bcl-XL overexpression inhibits taxol-induced Yama protease activity and apoptosis.
Cell Growth & Differentiation 1996; 7: 1087–1094. Copyright information
© Kluwer Academic Publishers 2000