Inhibition of specificity protein 1 by dibenzylideneacetone, a curcumin analogue, induces apoptosis in mucoepidermoid carcinomas and tumor xenografts through Bim and truncated Bid.
Oral Oncol
; 50(3): 189-95, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24309154
ABSTRACT
OBJECTIVES:
Dibenzylideneacetone (DBA), a curcumin analogue that has anti-cancer activity in a variety of tumor cells. In this study, we investigated the apoptotic effects of DBA and its molecular mechanism in human mucoepidermoid carcinoma (MEC) cell lines and tumor xenografts. MATERIAL ANDMETHODS:
The apoptotic effects and related molecular mechanisms of DBA on MEC cell lines were evaluated using cell viability assay, DAPI staining, Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and Dual-luciferase Reporter Assay. The anti-tumor activity using in vivo were determined by Nude mouse xenograft assay and histopathological examination.RESULTS:
DBA decreased cell viability and induced apoptosis in MEC cells. These events were accompanied by inhibition of specificity protein 1 (Sp1). DBA did not induce major changes in Sp1 mRNA and promoter activity. Furthermore, inhibition of protein synthesis by cycloheximide demonstrated that DBA decreased Sp1 protein stability, but DBA did not attenuate phosphorylation of eIF4E. DBA also increased Bim and truncated Bid (t-Bid) via Sp1. Finally, DBA exhibited significant anti-tumor activity in athymic nude mice xenografts bearing MC-3 cells by regulating Sp1, Bim and t-Bid without any systemic toxicity.CONCLUSION:
These results elucidate a crucial apoptotic mechanism of DBA and suggest that DBA may be a potent anticancer drug candidate for MEC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pentanonas
/
Fator de Transcrição Sp1
/
Carcinoma Mucoepidermoide
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
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Humans
Idioma:
En
Revista:
Oral Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2014
Tipo de documento:
Article