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


CONCLUSIONS
Glioma cell lines are refractory to the induction of differentiation or apoptosis by retinoids.
Schmidt
F
F
Laboratory of Molecular Neuro-Oncology, Department of Neurology, University of Tübingen, School of Medicine, Tübingen, Germany.
Groscurth
P
P
Dichgans
J
J
Weller
M
M
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000187:drug effects; D002454:Cell Differentiation; D004347:Drug Interactions; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism; D014212:Tretinoin / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016898:Interferon-alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014212:Tretinoin; D007371:Interferon-gamma