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Cilengitide induces autophagy-mediated cell death in glioma cells

Stephanie L Lomonaco1, Susan Finniss, Cunli Xiang

  • 1William and Karen Davidson Laboratory of Cell Signaling and Tumorigenesis, Detroit, MI 48202, USA.

Neuro-Oncology
|July 27, 2011
PubMed

Insights

The integrin inhibitor cilengitide causes glioma cell death by inducing autophagy and apoptosis. Cilengitide also enhances the effects of radiation therapy on glioma stem-like cells.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Glioma is an aggressive brain tumor with limited treatment options.
  • Integrins play a role in glioma cell proliferation, migration, and survival.
  • Targeting integrins offers a potential therapeutic strategy for glioma.

Purpose of the Study:

  • To investigate the effects of the integrin inhibitor cilengitide on glioma cells, including glioma stem-like cells (GSCs).
  • To determine the role of autophagy in cilengitide's cytotoxic effects.
  • To evaluate cilengitide's potential to sensitize glioma cells to radiation therapy.

Main Methods:

  • Treatment of human glioma cells and GSCs with cilengitide.
  • Assessment of cell viability, detachment, and apoptosis.
  • Induction and inhibition of autophagy.
  • Combination treatment with cilengitide and gamma irradiation.
  • Evaluation of cell renewal in GSCs.

Main Results:

  • Cilengitide induced cell detachment, decreased cell viability, and triggered autophagy followed by apoptosis in glioma cells.
  • Cilengitide reduced the self-renewal capacity of GSCs.
  • Inhibition of autophagy diminished cilengitide's cytotoxic impact.
  • Pretreatment with cilengitide enhanced autophagy and radiosensitivity in glioma cells and GSCs.

Conclusions:

  • Cilengitide exhibits cytotoxic effects against glioma cells and GSCs, partly mediated by autophagy induction.
  • Cilengitide sensitizes glioma cells to gamma irradiation, suggesting a potential combination therapy approach.
  • Targeting integrins with cilengitide represents a promising strategy for glioma treatment.

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