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 alpha (IFN-alpha) was investigated in PC-3 human prostate carcinoma cell line. IFN-alpha 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-alpha. Transforming growth factor beta (TGF-beta) significantly inhibited PC-3 cell growth, and the effect was additived to that of IFN-alpha. TGF-beta content in conditioned medium of PC-3 cells was not affected by treatment with IFN-alpha. On the other hand, IFN-alpha 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-alpha 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-alpha.