Evaluation of the effect of suramin on neural cell growth and N-CAM expression

Abstract

Suramin, a polysulfonated naphthylurea, is currently under investigation for treatment of advanced malignancy and has been shown to exhibit antiproliferative effects on some cells. We investigated its action on two cell lines of neural origin, one with neuronal (N2A) and the other with glial (C6) phenotype, as well as on brain primary cultures. We showed that suramin completely inhibited astrocytoma proliferation for an optimal dose of 1000 micrograms/ml but had the opposite effect on neuroblastoma cells. For these cells, doses as low as 12.5 micrograms/ml first increased cell proliferation and then led to massive cell death. This cytotoxic effect, which could be compatible with an internalization of the drug by the cells, was also observed for postmitotic neurons in brain primary cultures. In both cell lines, suramin was responsible for an accumulation of the neural cell adhesion molecule at the cell surface. One of the causes was the inhibition by suramin on the liberation processes of the phosphatidylinositol anchored Mr 120,000 isoform. At the mRNA level, suramin (12.5 to 50 micrograms/ml) induced an increase of all neural cell adhesion molecule transcripts in N2A but not in C6 cells. Suramin did not have an overall effect on transcription rates or RNA stability as the levels of transcripts coding for PrPc, another cell surface molecule, and actin were not affected. Our data demonstrated pleiotropic action of suramin. The neurotoxic effect exerted on neurons needs to be considered as possible outcomes for the use of suramin in humans.