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

Paclitaxel and docetaxel are potent anti-microtubule and antimitotic agents that induce apoptosis in bone marrow-derived cells and epithelial cells. T his study examined apoptosis induced by anti-microtubule agents in the neur oblastoma SK-N-SH cell line with a special focus on tau protein which is on e of the main Microtubule-Associated- Proteins (MAPs) in neuronal cells. In time, treatment with 1 mu M paclitaxel successively induced formation of b undles, then pseudo-asters concomitantly with mitotic block and phosphoryla tion of bcl-2 (48 h), then phosphorylation of tau and externalization of ph osphatidylserine at the early phase of apoptosis (72 h) and finally DNA fra gmentation (96 h). Similar results were obtained with 0.5 mu M vinorelbine. Paclitaxel induced a lower increase in tau phosphorylation in differentiat ed SK-N-SH/RA+ cells which are less sensitive to apoptosis. Moreover, doxor ubicin whose mechanism of action is independent of microtubules also induce d immunostaining of tau at 72 h treatment. In conclusion, our results on ne uroblastoma cells show that overexpression of hyperphosphorylated tau is in volved in the apoptotic process induced by anti-microtubule agents and may be extended to others cytostatic drugs. Thus, tau protein may play a role i n the cellular events observed in neuroblastoma cells undergoing apoptosis.