TRAIL-induced apoptosis in gliomas is enhanced by Akt-inhibition and is independent of JNK activation
Φόρτωση...
Ημερομηνία
Συγγραφείς
Puduvalli, V. K.
Sampath, D.
Bruner, J. M.
Nangia, J.
Xu, R.
Kyritsis, A. P.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Apoptosis
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
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.
Περιγραφή
Λέξεις-κλειδιά
*Apoptosis, Apoptosis Regulatory Proteins, Cell Line, Tumor, Enzyme Activation, Glioma/*pathology, Humans, JNK Mitogen-Activated Protein Kinases/*metabolism, MAP Kinase Kinase 4, Membrane Glycoproteins/*physiology, Mitogen-Activated Protein Kinase Kinases/*metabolism, Protein-Serine-Threonine Kinases/*antagonists & inhibitors, Proto-Oncogene Proteins/*antagonists & inhibitors, Proto-Oncogene Proteins c-akt, Signal Transduction, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha/*physiology
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/15711939
http://www.springerlink.com/content/v514l54633t42674/fulltext.pdf
http://www.springerlink.com/content/v514l54633t42674/fulltext.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής