Effects of combinations of interferon-βser and interferon-γ on interferon-inducible proteins and on the cell cycle

J. H. Schiller, M. A. Horisberger, G. Bittner, J. M. Carlin, B. Storer, G. I. Byrne, J. K V Willson, E. C. Borden

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

SKCO 1 human colon carcinoma cells have been shown to be synergistically inhibited in their growth by the combinations of α-interferon (IFN-α) or β-interferon (IFN-βser) and γ-interferon (IFN-γ). To determine if a correlation could be established between this synergistic antiproliferative effect and a synergistic induction in IFN-inducible proteins, or a unique perturbation in the cell cycle, we studied the effects of IFN-βser and IFN-γ, alone and in combination, on 2′,5′-oligoadenylate (2-5A) synthetase, indoleamine-2,3-dioxygenase (IDO), a human analogue of the murine Mx protein (p78), and the phases of cell cycle. 2-5A synthetase was maximally induced after a 24-h exposure to both IFN-β and IFN-γ. A synergistic enhancement of 2-5A synthetase activity was observed only with low concentration of each IFN (0.05 ng/ml). IDO activity was induced by IFN-γ and the combination of IFN-βser and IFN-γ, but not IFN-βser alone. The differences in IDO activity between IFN-γ and the combination, however, were not statistically significant. The p78 protein was induced in a dose-dependent manner by IFN-α and IFN-βser, IFN-γ enhanced the expression of p78 induction by IFN-α or IFN-βser, even at concentrations of IFN-γ that did not induce the protein when administered as a single agent. The combination of IFN-α and IFN-βser, which results in an antagonstic antiproliferative effect, also resulted in an antagonistic induction of p78. No changes in the cell cycle were observed following exposure to IFN-βser, IFN-γ, or the combination, and treatment with IFN-γ did not inhibit the accumulation of cells in G2M caused by colchicine. Thus, the synergistic antiproliferative effect produced by IFN-βser and IFN-γ in SKCO 1 cells could not be correlated with a synergistic enhancement in 2-5A synthetase or IDO activity, or with a perturbation in the cell cycle. In contrast, the combination of IFN-γ and IFN-α or IFN-βser synergistically enhanced the expression of p78 protein in these cells.

Original languageEnglish (US)
Pages (from-to)368-377
Number of pages10
JournalJournal of Biological Response Modifiers
Volume9
Issue number4
StatePublished - Aug 1990

Keywords

  • Cell cycle
  • Human colon carcinoma cells
  • Interferon-α
  • Interferon-β
  • Interferon-γ
  • Proteins

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Cancer Research

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    Schiller, J. H., Horisberger, M. A., Bittner, G., Carlin, J. M., Storer, B., Byrne, G. I., Willson, J. K. V., & Borden, E. C. (1990). Effects of combinations of interferon-βser and interferon-γ on interferon-inducible proteins and on the cell cycle. Journal of Biological Response Modifiers, 9(4), 368-377.