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Tau protein is involved in the apoptotic process induced by anti-microtubule agents on neuroblastoma cells

S Guise1, D Braguer, M Remacle-Bonnet

  • 1UPRES-A CNRS 6032, Université de la Méditerranée, Marseille, France.

Apoptosis : an International Journal on Programmed Cell Death
|November 25, 2003
PubMed

Insights

Anti-microtubule chemotherapy agents induce apoptosis in neuroblastoma cells by promoting tau protein hyperphosphorylation. This tau modification is linked to cell death, suggesting a role in drug-induced apoptosis.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Pharmacology

Background:

  • Paclitaxel and docetaxel are established anti-microtubule and antimitotic drugs.
  • These agents induce apoptosis in various cell types, including bone marrow and epithelial cells.
  • Neuroblastoma is a pediatric cancer with significant unmet therapeutic needs.

Purpose of the Study:

  • To investigate apoptosis induced by anti-microtubule agents in the neuroblastoma SK-N-SH cell line.
  • To specifically examine the role of tau protein, a key Microtubule-Associated Protein (MAP), in this process.
  • To understand the temporal sequence of events leading to apoptosis.

Main Methods:

  • Treatment of SK-N-SH cells with paclitaxel (1 microM) or vinorelbine (0.5 microM).
  • Assessment of cellular events including microtubule bundling, pseudo-aster formation, mitotic block, bcl-2 phosphorylation, tau phosphorylation, phosphatidylserine externalization, and DNA fragmentation.
  • Comparison of drug effects on differentiated, less sensitive SK-N-SH/RA+ cells.
  • Investigation of doxorubicin's effect on tau immunostaining.

Main Results:

  • Paclitaxel treatment induced a cascade of events: microtubule bundling, pseudo-asters, mitotic block, bcl-2 phosphorylation (48h), tau phosphorylation and phosphatidylserine externalization (72h), and DNA fragmentation (96h).
  • Similar results were observed with vinorelbine.
  • Differentiated SK-N-SH/RA+ cells showed reduced tau phosphorylation in response to paclitaxel.
  • Doxorubicin, a non-microtubule targeting agent, also induced tau immunostaining.

Conclusions:

  • Hyperphosphorylated tau is implicated in the apoptotic process of neuroblastoma cells treated with anti-microtubule agents.
  • The findings suggest that tau protein plays a significant role in the cellular events of apoptosis in neuroblastoma.
  • The observed tau hyperphosphorylation may extend to other cytostatic drug treatments.

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