Induction of brain tumor stem cell apoptosis by FTY720: a potential therapeutic agent for glioblastoma.
Neuro Oncol
; 14(4): 405-15, 2012 Apr.
Article
em En
| MEDLINE
| ID: mdl-22351749
ABSTRACT
FTY720 is a sphingosine analogue that down regulates expression of sphingosine-1-phosphate receptors and causes apoptosis of multiple tumor cell types, including glioma cells. This study examined the effect of FTY720 on brain tumor stem cells (BTSCs) derived from human glioblastoma (GBM) tissue. FTY720 treatment of BTSCs led to rapid inactivation of ERK MAP kinase, leading to upregulation of the BH3-only protein Bim and apoptosis. In combination with temozolomide (TMZ), the current standard chemotherapeutic agent for GBM, FTY720 synergistically induced BTSC apoptosis. FTY720 also slowed growth of intracranial xenograft tumors in nude mice and augmented the therapeutic effect of TMZ, leading to enhanced survival. Furthermore, the combination of FTY720 and TMZ decreased the invasiveness of BTSCs in mouse brains. FTY720 is known to cross the blood-brain barrier and recently received Food and Drug Administration approval for treatment of relapsing multiple sclerosis. Thus, FTY720 is an excellent potential therapeutic agent for treatment of GBM.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Propilenoglicóis
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Esfingosina
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Células-Tronco Neoplásicas
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Proteínas Proto-Oncogênicas
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MAP Quinases Reguladas por Sinal Extracelular
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Receptores de Lisoesfingolipídeo
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Proteínas Reguladoras de Apoptose
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Proteínas de Membrana
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article