Suppression of autophagy enhanced growth inhibition and apoptosis of interferon-β in human glioma cells

Mol Neurobiol. 2013 Jun;47(3):1000-10. doi: 10.1007/s12035-013-8403-0. Epub 2013 Jan 18.

Abstract

Interferon-beta (IFN-β) is a cytokine with anti-viral, anti-proliferative, and immunomodulatory effects. In this study, we investigated the effects of IFN-β on the induction of autophagy and the relationships among autophagy, growth inhibition, and apoptosis induced by IFN-β in human glioma cells. We found that IFN-β induced autophagosome formation and conversion of microtubule associated protein 1 light chain 3 (LC3) protein, whereas it inhibited cell growth through caspase-dependent cell apoptosis. The Akt/mTOR signaling pathway was involved in autophagy induced by IFN-β. A dose- and time-dependent increase of p-ERK 1/2 expression was also observed in human glioma cells treated with IFN-β. Autophagy induced by IFN-β was suppressed when p-ERK1/2 was impaired by treatment with U0126. We also demonstrated that suppression of autophagy significantly enhanced growth inhibition and cell apoptosis induced by IFN-β, whereas inhibition of caspase-dependent cell apoptosis impaired autophagy induced by IFN-β. Collectively, these findings indicated that autophagy induced by IFN-β was associated with the Akt/mTOR and ERK 1/2 signaling pathways, and inhibition of autophagy could enhance the growth inhibitory effects of IFN-β and increase apoptosis in human glioma cells. Together, these findings support the possibility that autophagy inhibitors may improve IFN-β therapy for gliomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Glioma / enzymology
  • Glioma / pathology*
  • Glioma / ultrastructure
  • Humans
  • Interferon-beta / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Phagosomes / drug effects
  • Phagosomes / metabolism
  • Phagosomes / ultrastructure
  • Proto-Oncogene Proteins c-akt / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Interferon-beta
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt