Human Malignant Glioma Cell Lines are Refractory to Retinoic Acid-Mediated Differentiation and Sensitization to Apoptosis1

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Abstract
Retinoids are candidate differentiation-inducing agents for glial tumors. Differentiation therapy is an attractive approach to cancers that resist surgery, irradiation and chemotherapy. We examined the effects of retinoids on proliferation, morphology and sensitivity to apoptosis in human malignant glioma and neuroblastoma cell lines. 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. Glioma cell lines are refractory to the induction of differentiation or apoptosis by retinoids.

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