Antitumor activity of a novel histone deacetylase inhibitor (S)-HDAC42 in oral squamous cell carcinoma.
Oral Oncol
; 47(12): 1127-33, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-21865079
ABSTRACT
The aberrant regulation of epigenetic systems including histone acetylation contributes to inappropriate gene expression in cancer cells. In this study, we investigated the antitumor effects of the novel histone deacetylase inhibitor (S)-HDAC42 in oral squamous cell carcinoma (OSCC) cells. The antiproliferative effect of (S)-HDAC42 was multifold higher than that of suberoylanilide hydroxamic acid in a panel of oral squamous carcinoma cell lines examined. (S)-HDAC42 mediated caspase-dependent apoptosis by targeting multiple signaling pathways relevant to cell cycle progression and survival. We demonstrated that (S)-HDAC42 downregulated the levels of phospho-Akt, cyclin D1, and cyclin-dependent kinase 6, accompanied by increased p27 and p21 expression. In addition, (S)-HDAC42 suppressed NF-κB signaling by blocking tumor necrosis factor-α-induced nuclear translocation, and activated reactive oxygen species generation. Finally, (S)-HDAC42 exhibited high potency in suppressing OSCC tumor growth in a Ca922 xenograft nude mouse model. Together, these findings underscore the translational value of (S)-HDAC42 in fostering new therapeutic strategies for OSCC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenilbutiratos
/
Neoplasias Bucais
/
Carcinoma de Células Escamosas
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Inibidores de Histona Desacetilases
/
Ácidos Hidroxâmicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Oral Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Taiwan
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM