Effects of interferon and PKC modulators on human glioma protein kinase C, cell proliferation, and cell cycle

Neurochem Res. 1997 Jul;22(7):775-84. doi: 10.1023/a:1022071407268.

Abstract

The in-vitro effects of human interferon alpha-2b (HuIFN alpha-2b), protein kinase C (PKC) agonist [TPA (12-0-tetra-decanoyl-phorbol-13-acetate)] and PKC inhibitor (calphostin C) on human glioma (U-373 MG) PKC activity, cell proliferation and cell cycle were compared. HuIFN alpha-2b and TPA increased PKC activity, elevated the number of cells in DNA synthesis (S) phase and decreased cell proliferation by similar magnitudes. Calphostin C inhibited PKC activity, increased the number of cells in S phase and produced strong cytotoxic effects (IC50 150 nM). Higher concentrations of calphostin C with or without serum induced an additional block in gap2 and mitosis. We conclude that HuIFN alpha-2b's mode of action may be directly or indirectly affecting PKC. The response produced by HuIFN alpha-2b is similar to TPA (potent PKC activation and S phase arrest).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Drug Screening Assays, Antitumor
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Glioma / drug therapy*
  • Glioma / enzymology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Naphthalenes / pharmacology
  • Protein Kinase C / drug effects*
  • Recombinant Proteins
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Interferon alpha-2
  • Interferon-alpha
  • Naphthalenes
  • Recombinant Proteins
  • Protein Kinase C
  • calphostin C
  • Tetradecanoylphorbol Acetate