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

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 mu M, inhibited apoptosis in growth-factor deprived cells as demonstrated by inhibition of DNA fragmentation and increased cell survival. ATA, at a concentration of 25 mu M 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. (C) 1999 Elsevier Science B.V. All rights reserved.