title: 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.
authors.affiliation: Department of Urology, Kagawa Medical School Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okutani
authors.forename: N
authors.initials: N
authors.lastname: Nishi
authors.forename: Y
authors.initials: Y
authors.lastname: Kagawa
authors.forename: H
authors.initials: H
authors.lastname: Takasuga
authors.forename: I
authors.initials: I
authors.lastname: Takenaka
authors.forename: T
authors.initials: T
authors.lastname: Usui
authors.forename: F
authors.initials: F
authors.lastname: Wada
mesh_terms: 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
chemical_list: 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