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Vol. 20, No. 1-4, 2007
Issue release date: 2007
Section title: Original Paper
Cell Physiol Biochem 2007;20:023–034

Mechanisms of Resistance of Human Glioma Cells to Apo2 Ligand/TNF-Related Apoptosis-Inducing Ligand

Rieger J.1 · Frank B.1 · Weller M.1 · Wick W.1,2
1Laboratory of Molecular Neuro-Oncology, Department of General Neurology and Hertie Insitute for Clinical Brain Research, University of Tuebingen2Department of Neurooncology, University of Heidelberg

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Background: Many tumor cells are resistant to Apo2L/TRAIL-induced apoptosis in the absence of inhibitors of protein synthesis. Apo2L/TRAIL, in addition to induction of apoptosis, may therefore also activate survival pathways. Methods: Here we investigated whether such survival pathways mediate resistance to Apo2L.0-induced apoptosis in human glioma cells. Results: Apo2L.0 induced the phosphorylation of ERK1/2, but not of Akt. This effect was unaffected by caspase inhibition. Inhibitors of protein synthesis, PI3 kinase, ERK kinase, NF-ĸB or casein kinase 2 sensitized for Apo2L.0-induced apoptosis to a different extent in a panel of human malignant glioma cell lines. However, none of the sensitizers overcame resistance mediated by ectopic expression of the viral caspase 8 inhibitor, crm-A. Primary glioma cultures were almost completely resistant to Apo2L.0-induced cell death even in the presence of the inhibitors. Caspase-8 was expressed in these cells whereas only weak expression of DR5 was detected. Transient expression of DR5 conferred sensitivity to Apo2L.0. Conclusion: These data challenge the view that specific cell lines harbour specific mechanisms of resistance to Apo2L/TRAIL. Weak expression of DR5 in primary glioma might limit the therapeutic application of Apo2L/TRAIL in human glioblastoma patients.

© 2007 S. Karger AG, Basel


Author Contacts

Wolfgang Wick
Lab Mol Neurooncol, Institute for Clinical Brain Research
Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany)
Tel. +49 7071 29 80416, Fax: +49 7071 29 5260


Article Information

Accepted: January 09, 2007
Number of Print Pages : 12


Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 20, No. 1-4, Year 2007 (Cover Date: 2007)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (print), 1421–9778 (Online)

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: 5/22/2007
Issue release date: 2007

Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

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Copyright / Drug Dosage

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