Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers.

Détails

Ressource 1Télécharger: BIB_FEDD07A04B15.P001.pdf (724.35 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_FEDD07A04B15
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers.
Périodique
Plos One
Auteur(s)
Chevalier N., Gross N., Widmann C.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
10
Numéro
3
Pages
e0120487
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Résumé
Although current anti-cancer protocols are reasonably effective, treatment-associated long-term side effects, induced by lack of specificity of the anti-cancer procedures, remain a challenging problem in pediatric oncology. TAT-RasGAP317-326 is a RasGAP-derived cell-permeable peptide that acts as a sensitizer to various anti-cancer treatments in adult tumor cells. In the present study, we assessed the effect of TAT-RasGAP317-326 in several childhood cancer cell lines. The RasGAP-derived peptide-induced cell death was analyzed in several neuroblastoma, Ewing sarcoma and leukemia cell lines (as well as in normal lymphocytes). Cell death was evaluated using flow cytometry methods in the absence or in the presence of the peptide in combination with various genotoxins used in the clinics (4-hydroperoxycyclophosphamide, etoposide, vincristine and doxorubicin). All tested pediatric tumors, in response to at least one genotoxin, were sensitized by TAT-RasGAP317-326. The RasGAP-derived peptide did not increase cell death of normal lymphocytes, alone or in combination with the majority of the tested chemotherapies. Consequently, TAT-RasGAP317-326 may benefit children with tumors by increasing the efficacy of anti-cancer therapies notably by allowing reductions in anti-cancer drug dosage and the associated drug-induced side effects.
Mots-clé
Age Factors, Antineoplastic Agents/pharmacology, Case-Control Studies, Cell Death/drug effects, Cell Line, Tumor, Drug Resistance, Neoplasm, Drug Synergism, GTPase-Activating Proteins/pharmacology, Humans, Inhibitory Concentration 50, Lymphocytes/drug effects, Mutagens/pharmacology, Neoplasms/pathology, Neuroblastoma, Peptide Fragments/pharmacology, Sarcoma, Ewing
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/04/2015 18:13
Dernière modification de la notice
20/08/2019 17:29
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