SNAP reverses temozolomide resistance in human glioblastoma multiforme cells through down-regulation of MGMT.
FASEB J
; 33(12): 14171-14184, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31725331
ABSTRACT
Glioblastoma multiforme (GBM) is the most frequently occurring and gravest primary tumor of the CNS in adults. The development of chemoresistance to temozolomide (TMZ), the first-line chemotherapy for GBM, is an important factor contributing to poor treatment outcomes. Down-regulation of O-6-methylguanine-DNA methyltransferase (MGMT) expression in GBM cells is an attractive strategy for overcoming TMZ resistance and improving outcomes. This study revealed that the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) exerts antitumorigenic effects on TMZ-sensitive and TMZ-resistant (TMZ-R) glioma cells. Pretreatment with SNAP not only induced apoptosis, mitochondrial dysfunction, and hypoxia-inducing factor 1, but also resensitized TMZ-R GBM cells to TMZ through down-regulation of MGMT expression. SNAP acted principally through post-translational modification of p53, phosphorylated N-myc downstream regulated gene 1, and MGMT protein stability in TMZ-R GBM cells. Additionally, when applied together, SNAP and TMZ enhanced the inhibition of tumor growth in vitro and in vivo. This study sheds new light on a potential strategy to overcome TMZ resistance in GBM and thus possesses the potential for prolonging survival of patients with GBM.-Tsai, C.-K., Huang, L.-C., Wu, Y.-P., Kan, I.-Y., Hueng, D.-Y. SNAP reverses temozolomide resistance in human glioblastoma multiforme cells through down-regulation of MGMT.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Metilases de Modificação do DNA
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Glioblastoma
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Resistencia a Medicamentos Antineoplásicos
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S-Nitroso-N-Acetilpenicilamina
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Proteínas Supressoras de Tumor
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Enzimas Reparadoras do DNA
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Temozolomida
Limite:
Animals
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Humans
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
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FISIOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Taiwan