Aurintricarboxylic acid inhibits apoptosis and supports proliferation in a haemopoietic growth-factor dependent myeloid cell line

Abstract

The actions of the nuclease inhibitor aurintricarboxylic acid (ATA) were investigated in the growth-factor dependent murine myeloid cell line NSF-60. NSF-60 cells proliferate in response to interleukin-3 (IL-3) and undergo apoptosis when deprived of exogenous IL-3, as demonstrated by the appearance of characteristic DNA 'ladders' following agarose gel electrophoresis. ATA, at concentrations between 5 and 25 microM, inhibited apoptosis in growth-factor deprived cells as demonstrated by inhibition of DNA fragmentation and increased cell survival. ATA at a concentration of 25 microM supported proliferation of the cell line in the absence of exogenous growth-factor. Both ATA and IL-3 increased protein phosphorylation in this cell line. ATA and IL-3 induced proliferation was inhibited by the kinase inhibitors genistein, staurosporine and H-7. These findings suggest that, in NSF-60, ATA is not acting exclusively as an endonuclease inhibitor and that protein phosphorylation is involved in the mechanism of action of ATA in this cell line.