Human malignant glioma cell lines are refractory to retinoic acid-mediated differentiation and sensitization to apoptosis

Cell Physiol Biochem. 2000;10(3):159-68. doi: 10.1159/000016346.

Abstract

Background: Retinoids are candidate differentiation-inducing agents for glial tumors. Differentiation therapy is an attractive approach to cancers that resist surgery, irradiation and chemotherapy.

Methods: We examined the effects of retinoids on proliferation, morphology and sensitivity to apoptosis in human malignant glioma and neuroblastoma cell lines.

Results: In contrast to neuroblastoma cells, retinoids are devoid of acute cytotoxic effects and have only moderate antiproliferative effects on human glioma cell lines upon long-term exposure at high concentrations. Electron microscopy fails to reveal features of differentiation or apoptosis in retinoid-treated glioma cells and untransformed rat astrocytes. Retinoids do not modulate CD95 or CD95L expression or susceptibility to CD95-mediated apoptosis and fail to act in synergy with interferon (IFN)-alpha or IFN-gamma or cancer chemotherapy drugs to promote growth inhibition or apoptosis.

Conclusion: Glioma cell lines are refractory to the induction of differentiation or apoptosis by retinoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Astrocytes / drug effects
  • Cell Differentiation
  • Drug Interactions
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Interferon-alpha / pharmacology
  • Interferon-gamma / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Stereoisomerism
  • Tretinoin / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Interferon-alpha
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Tretinoin
  • Interferon-gamma