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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2005-2-15
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pubmed:abstractText |
Patients with malignant gliomas have a poor prognosis and new treatment paradigms are needed against this disease. TRAIL/Apo2L selectively induces apoptosis in malignant cells sparing normal cells and is hence of interest as a potential therapeutic agent against gliomas. To determine the factors that modulate sensitivity to TRAIL, we examined the differences in TRAIL-activated signaling pathways in glioma cells with variable sensitivities to the agent. Apoptosis in response to TRAIL was unrelated to DR5 expression or endogenous p53 status in a panel of 8 glioma cell lines. TRAIL activated the extrinsic (cleavage of caspase-8, caspase-3 and PARP) and mitochondrial apoptotic pathways and reduced FLIP levels. It also induced caspase-dependent JNK activation, which did not influence TRAIL-induced apoptosis. Because the pro-survival PI3K/Akt pathway is highly relevant to gliomas, we assessed whether Akt could protect against TRAIL-induced apoptosis. Pretreatment with SH-6, a novel Akt inhibitor, enhanced TRAIL-induced apoptosis, suggesting a protective role for Akt. Conversely, TRAIL induced caspase-dependent cleavage of Akt neutralizing its anti-apoptotic effects. These results demonstrate that TRAIL-induced apoptosis in gliomas involves both activation of death pathways and downregulation of survival pathways. Additional studies are warranted to determine the therapeutic potential of TRAIL against gliomas.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1360-8185
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
233-43
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pubmed:dateRevised |
2011-9-22
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pubmed:meshHeading |
pubmed-meshheading:15711939-Apoptosis,
pubmed-meshheading:15711939-Apoptosis Regulatory Proteins,
pubmed-meshheading:15711939-Cell Line, Tumor,
pubmed-meshheading:15711939-Enzyme Activation,
pubmed-meshheading:15711939-Glioma,
pubmed-meshheading:15711939-Humans,
pubmed-meshheading:15711939-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:15711939-MAP Kinase Kinase 4,
pubmed-meshheading:15711939-Membrane Glycoproteins,
pubmed-meshheading:15711939-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:15711939-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15711939-Proto-Oncogene Proteins,
pubmed-meshheading:15711939-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15711939-Signal Transduction,
pubmed-meshheading:15711939-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:15711939-Tumor Necrosis Factor-alpha
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pubmed:year |
2005
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pubmed:articleTitle |
TRAIL-induced apoptosis in gliomas is enhanced by Akt-inhibition and is independent of JNK activation.
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pubmed:affiliation |
Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 7700, USA. vpuduval@mdanderson.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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