Linked Life Data

16957768

Source:http://linkedlifedata.com/resource/pubmed/id/16957768

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-4
pubmed:abstractText
The expression of inhibitor of apoptosis (IAP) family members contributes to the resistance of human cancers to apoptosis induced by radiotherapy and chemotherapy. We report that the infection of malignant glioma cells and several other tumor cell lines with adenoviruses encoding antisense RNA to X-linked IAP (XIAP) depletes endogenous XIAP levels and promotes global caspase activation and apoptosis. In contrast, non-neoplastic SV-FHAS human astrocytes and other non-neoplastic cells express XIAP at very low levels and resist these effects of adenovirus-expressing XIAP antisense RNA (Ad-XIAP-as). Caspase inhibitors such as z-Val-Ala-DL-Asp(OMe)-fluoromethylketone (zVAD-fmk) delay caspase processing and XIAP depletion, suggesting that XIAP depletion results both from antisense-mediated interference with protein synthesis and proteolytic cleavage by activated caspases. However, zVAD-fmk neither prevents nor delays cell death, indicating a caspase-independent pathway to cell death triggered by IAP depletion. Similarly, B-cell lymphoma-X(L) (BCL-X(L)) inhibits caspase activity, but fails to rescue from apoptosis. Loss of p65/nuclear factor-kappaB (NF-kappaB) protein and NF-kappaB activity is an early event triggered by Ad-XIAP-as and probably involved in Ad-XIAP-as-induced apoptosis. Finally, Ad-XIAP-as gene therapy induces cell death in intracranial glioma xenografts, prolongs survival in nude mice and may reduce tumorigenicity in synergy with Apo2L/TNF-related apoptosis-inducing ligand (TRAIL) in vivo. Altogether, these data define a powerful survival function for XIAP and reinforce its possible role as a therapeutic target in human glioma cells.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
147-61
pubmed:dateRevised
2007-10-24
pubmed:meshHeading
pubmed-meshheading:16957768-Adenoviridae, pubmed-meshheading:16957768-Amino Acid Chloromethyl Ketones, pubmed-meshheading:16957768-Animals, pubmed-meshheading:16957768-Apoptosis, pubmed-meshheading:16957768-Caspases, pubmed-meshheading:16957768-Enzyme Activation, pubmed-meshheading:16957768-Female, pubmed-meshheading:16957768-Gene Expression, pubmed-meshheading:16957768-Gene Therapy, pubmed-meshheading:16957768-Genetic Vectors, pubmed-meshheading:16957768-Glioma, pubmed-meshheading:16957768-Humans, pubmed-meshheading:16957768-Immunohistochemistry, pubmed-meshheading:16957768-Mice, pubmed-meshheading:16957768-Mice, Nude, pubmed-meshheading:16957768-NF-kappa B, pubmed-meshheading:16957768-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:16957768-RNA, Antisense, pubmed-meshheading:16957768-X-Linked Inhibitor of Apoptosis Protein, pubmed-meshheading:16957768-Xenograft Model Antitumor Assays
pubmed:year
2007
pubmed:articleTitle
Adenoviral expression of XIAP antisense RNA induces apoptosis in glioma cells and suppresses the growth of xenografts in nude mice.
pubmed:affiliation
Laboratory of Molecular Neuro-Oncology, Department of General Neurology, Hertie Institute for Clinical Brain Research, Tübingen, Germany. ulrike.naumann@uni-tuebingen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't