Inhibition of myeloid cell leukemia-1: Association with sorafenib-induced apoptosis in human mucoepidermoid carcinoma cells and tumor xenograft.
Head Neck
; 37(9): 1326-35, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-25043125
ABSTRACT
BACKGROUND:
The purpose of our study was to investigate the anticancer effect of sorafenib on mucoepidermoid carcinoma (MEC) and find its new molecular mechanism.METHODS:
The apoptotic effects of sorafenib were performed using MTS assay, diamidino-phenylindole (DAPI) staining, Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), siRNA, and xenograft.RESULTS:
Sorafenib had apoptotic effects on MC-3 and YD15 cells and decreased myeloid cell leukemia-1 (Mcl-1) through proteasome-dependent protein degradation and the inhibition of protein synthesis. Sorafenib significantly affected truncated bid (t-Bid) and siMcl-1 resulting in the upregulation of t-Bid to induce apoptosis. Signal transducer and activator of transcription 3 (STAT3) phosphorylation was also blocked by sorafenib and a potent STAT3 inhibitor, cryptotanshinone clearly induced poly ADP-ribose polymerase (PARP) cleavage by inhibiting Mcl-1 and increasing t-Bid. Finally, administration of sorafenib significantly suppressed tumor growth and induced apoptosis in tumor xenograft model in association with downregulation of Mcl-1 without any side effects.CONCLUSION:
Taken together, these findings suggest that sorafenib can be a good anticancer drug candidate for the treatment of MEC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Leucemia
Base de dados:
MEDLINE
Assunto principal:
Compostos de Fenilureia
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Apoptose
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Niacinamida
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Proliferação de Células
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Proteína de Sequência 1 de Leucemia de Células Mieloides
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Head Neck
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2015
Tipo de documento:
Article