Effects of extracellular nucleotides and nucleosides on prostate carcinoma cells

Abstract

1. The purpose of this work was to characterize the receptors involved in the action of nucleotides on the human prostate carcinoma cell lines LNCaP, PC-3 and DU145. 2. Northern blotting revealed the presence of P2Y2, P2Y6 and P2Y11 messengers in the three cell lines. P2Y1 mRNA was only observed in the DU145 cells. In both PC-3 and DU145 cells, ATP and UTP stimulated inositol phosphate accumulation in an equipotent, equiactive and non-additive way, suggesting the involvement of P2Y2 receptors. ATP also increased cyclic AMP, but this effect is likely to result from degradation into adenosine and activation of A2 receptor. A2 receptor activation led to a synergistic enhancement of prostate-specific antigen secretion induced by vasoactive intestinal peptide. 3. RT-PCR experiments detected the expression of the P2X4 and P2X5 receptors in the DU145 cells and the P2X4, P2X5 and P2X7 receptors in the PC-3 cells. The calcium influx induced by BzATP confirmed the functional expression of P2X receptors. 4. ATP inhibited the growth of PC-3 and DU145 cells. This effect was mimicked neither by UTP nor by adenosine, indicating that it does not result from phospholipase C or adenylyl cyclase activation. On the contrary, in PC-3 cells, BzATP reproduced the effect of ATP, which was associated to a moderate decrease of proliferation and an increase of apoptosis. In DU145 cells, ATP was more potent than BzATP and growth inhibition was mainly associated with necrosis. We suggest that P2X receptors might be involved in the inhibition by nucleotides of prostate carcinoma cell growth.