Journal
NEUROBIOLOGY OF DISEASE
Volume 33, Issue 2, Pages 243-249Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2008.10.005
Keywords
Glioma; TRAIL/Apo2L; Survivin; HSP90; 17-AAG; Proteasome
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Funding
- University of Heidelberg
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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. (C) 2008 Elsevier Inc. All rights reserved.
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