CHARACTERIZATION OF THE CELL-DEATH PROCESS-INDUCED BY STAUROSPORINE IN HUMAN NEUROBLASTOMA CELL-LINES

Staurosporine is a potent and non-specific inhibitor of protein kinase s. There is also evidence of staurosporine being a potent inducer of a poptosis. In several human neuroblastoma cell lines (SH-SY5Y, NB69, IM R-5 and IMR-32) we have found 100 nM staurosporine to induce cell deat h in half the population (EC50) Electron microscopy of these cells, fl uorescence microscopy after Hoechst-33258 staining of chromatin and ag arose-electrophoresis of DNA, show two different types of cell death. SH-SY5Y and NB69 die by apoptosis and display all the characteristic f eatures of it. IMR-5 and IMR-32 lack some of these features and a ladd er pattern of DNA degradation is not found. Different morphological ty pes of apoptosis have been described during the development of vertebr ates; the possibility of finding a similar diversity in cell culture i s suggested. On the other hand, staurosporine is a potent promoter of neurite outgrowth. In all the neuroblastoma cell lines we have tested, neurite-promoting and cell death-inducing staurosporine concentration s mostly overlap. This fact has not been reported before, probably bec ause of an early versus late timing of these two different phenomena. The neuritogenic effect has prompted the suggestion that staurosporine could be a prototype of drugs for neurodegenerative diseases; the pre sent study raises several concerns about such a proposal. (C) 1997 Els evier Science Ltd.