Cell Growth & Differentiation, Vol 6, Issue 11 1375-1380, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Apoptosis induced by protein kinase C inhibition in a neuroblastoma cell line

MM Behrens, JL Martinez, C Moratilla and J Renart
Institute of Biomedical Investigations, Cosejo Superior de Investigaciones Cientificas, CSIC, Department of Biochemistry, Universidad Autonoma de Madrid, Spain.

The protein kinase C inhibitor bisindolylmaleimide GF109203X has a dual effect on the behavior of the neuroblastoma cell line Neuro-2A; when the inhibitor is added in conditions that induce differentiation (absence of serum), neurite outgrowth is potentiated in a dose-dependent manner. However, if the inhibitor is added in growth-promoting conditions (presence of serum), programmed cell death (apoptosis) is induced, as assessed by internucleosomal DNA cleavage and specific immunoassays. This effect is also seen with other specific protein kinase C inhibitors. Bcl2 gene overexpression protects Neuro-2A cells from apoptosis, as has been found in other systems. We also show that calpain I, a neutral Ca(2+)-activated proteinase, participates in this apoptotic pathway. Our results point to a key role of protein kinase C in the regulation of growth and differentiation in Neuro-2A cells.

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