17-AAG sensitized malignant glioma cells to death-receptor mediated apoptosis

17-AAG sensitized malignant glioma cells to death-receptor mediated apoptosis

17-AAG is a selective HSP90-inhibitor that exhibited therapeutic activity in cancer. In this study three glioblastoma cell lines (U87, LN229 and U251) were treated with 17-AAG, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of both. Treatment with subtoxic doses o...

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Bibliographic Details
Main Authors: Markus David Siegelin, Antje Habel, Timo Gaiser
Format: Article
Language:English
Published: Elsevier 2009-02-01
Series:Neurobiology of Disease
Subjects:
Glioma
TRAIL/Apo2L
Survivin
HSP90
17-AAG
Proteasome
Online Access:http://www.sciencedirect.com/science/article/pii/S096999610800260X
Description
Summary:17-AAG is a selective HSP90-inhibitor that exhibited therapeutic activity in cancer. In this study three glioblastoma cell lines (U87, LN229 and U251) were treated with 17-AAG, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of both. Treatment with subtoxic doses of 17-AAG in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant glioma cells, suggesting that this combined treatment may offer an attractive strategy for treating gliomas. 17-AAG treatment down-regulated survivin through proteasomal degradation. In addition, over-expression of survivin attenuated cytotoxicity induced by the combination of 17-AAG and TRAIL. In summary, survivin is a key regulator of TRAIL–17-AAG mediated cell death in malignant glioma.
ISSN:1095-953X

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