Role of cyclic AMP and polypeptide growth regulators in growth inhibition by interferon in PC-3 cells.
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.
Okutani
T
T
Department of Urology, Kagawa Medical School Japan.
Nishi
N
N
Kagawa
Y
Y
Takasuga
H
H
Takenaka
I
I
Usui
T
T
Wada
F
F
D000527:Alprostadil / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000473:pathology*; D015291:Transforming Growth Factors / Q000096:biosynthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006133:Growth Substances; D007370:Interferon Type I; D010982:Platelet-Derived Growth Factor; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D003994:Bucladesine; D015291:Transforming Growth Factors; D000242:Cyclic AMP; D000527:Alprostadil