Role of cyclic AMP and polypeptide growth regulators in growth inhibition by interferon in PC‐3 cells

Abstract
Participation of growth factors and intracellular cAMP in direct antiproliferative action of interferon α (IFN-α) was investigated in PC-3 human prostate carcinoma cell line. IFN-α inhibited proliferation of PC-3 cells in a dose-dependent manner in vitro, and the effect was reversible. Fibroblast growth factor, epidermal growth factor and platelet-derived growth factor, when added to the culture medium, showed no effect on growth of PC-3 cells in presence or absence of IFN-α. Transforming growth factor β (TGF-β) significantly inhibited PC-3 cell growth, and the effect was additived to that of IFN-α. TGF-β content in conditioned medium of PC-3 cells was not affected by treatment with IFN-α. On the other hand, IFN-α increased intracellular cAMP concentration about 20-fold. Dibutyryl cAMP and reagents which elevated intracellular cAMP level also inhibited PC-3 cell growth. These indicated that direct antiproliferative effect of IFN-α on PC-3 cells was at least partly mediated by cAMP, and that neither growth factors nor a growth inhibitor participated in the action of IFN-α.