Linked Life Data

17694433

Source:http://linkedlifedata.com/resource/pubmed/id/17694433

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2007-11-2
pubmed:abstractText
Glioblastoma is the deadliest and most prevalent brain tumor, which is not yet amenable to any treatments. Therefore, new and innovative therapeutic strategies need to be developed for treating this deadly disease. We found that all-trans retinoic acid (ATRA) or 13-cis retinoic acid (13-CRA) induced astrocytic differentiation with down regulation of telomerase activity in rat glioblastoma C6 cells and enhanced sensitivity of the cells to interferon-gamma (IFN-gamma) or taxol (TXL) for apoptosis. Sensitivity of differentiated cells to IFN-gamma or TXL was greatly increased for apoptosis with increases in calcineurin expression, Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and expression and activity of calpain and caspases. Treatment with IFN-gamma activated caspase-8 indicating induction of apoptosis via the receptor-mediated pathway. Notably, IFN-gamma activated the signal transducer and activator of transcription-1 (STAT-1) for signaling via binding to gamma activator sequence (GAS), whereas TXL activated Raf-1 kinase for inactivation of Bcl-2 by its phosphorylation. We confirmed involvement of different proteolytic mechanisms in cell death by pretreating the cells with caspase-8 inhibitor II, calpeptin (calpain inhibitor), and caspase-9 inhibitor I, and caspase-3 inhibitor IV. Results demonstrated that retinoids induced astrocytic differentiation with down regulation of telomerase activity and worked synergistically to enhance sensitivity of cells to the cytotoxic agent IFN-gamma and the cytostatic agent TXL for apoptosis. This combination therapy for differentiation and apoptosis could be highly effective for controlling the malignant growth of glioblastoma.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0364-3190
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2167-83
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17694433-Animals, pubmed-meshheading:17694433-Antineoplastic Agents, pubmed-meshheading:17694433-Antineoplastic Agents, Phytogenic, pubmed-meshheading:17694433-Apoptosis, pubmed-meshheading:17694433-Brain Neoplasms, pubmed-meshheading:17694433-Calcium, pubmed-meshheading:17694433-Caspase 8, pubmed-meshheading:17694433-Cell Differentiation, pubmed-meshheading:17694433-Cell Line, Tumor, pubmed-meshheading:17694433-DNA Fragmentation, pubmed-meshheading:17694433-Electrophoretic Mobility Shift Assay, pubmed-meshheading:17694433-Enzyme Activation, pubmed-meshheading:17694433-Glioblastoma, pubmed-meshheading:17694433-Interferon-gamma, pubmed-meshheading:17694433-Paclitaxel, pubmed-meshheading:17694433-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:17694433-Proto-Oncogene Proteins c-raf, pubmed-meshheading:17694433-Rats, pubmed-meshheading:17694433-Recombinant Proteins, pubmed-meshheading:17694433-Retinoids, pubmed-meshheading:17694433-Telomerase
pubmed:year
2007
pubmed:articleTitle
Differentiation decreased telomerase activity in rat glioblastoma C6 cells and increased sensitivity to IFN-gamma and taxol for apoptosis.
pubmed:affiliation
Department of Neurosciences, Medical University of South Carolina, P.O. Box 250606, Charleston, SC 29425, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural