Obatoclax induces Beclin 1- and ATG5-dependent apoptosis and autophagy in adenoid cystic carcinoma cells.
Oral Dis
; 21(4): 470-7, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25482163
ABSTRACT
OBJECTIVES:
Adenoid cystic carcinoma (ACC) is one of the most common salivary gland cancers. The prognosis of adenoid cystic carcinoma is poor for its high frequency of distant metastases and insensitivity to chemotherapy or molecular therapies. This study investigated the effect of Obatoclax on adenoid cystic carcinoma cells and its cytotoxic mechanism.METHODS:
Western blot, transmission electron microscopy, and pEGFP-LC3 plasmids transfection were carried out to detect autophagy in ACC cells treated with Obatoclax. 3-MA and RNA interference against Beclin 1 and ATG5 were used to inhibit autophagy. Then we used Western blot and Hochest 33342 staining for apoptosis assessment. Finally, cell viability was assessed by MTT assay.RESULTS:
We found that Obatoclax induced cytoprotective autophagy which depended on ATG5 and partly on Beclin 1 in adenoid cystic carcinoma cells. Furthermore, pharmacologically inhibiting Obatoclax-induced autophagy promoted apoptosis. Downregulation of Beclin 1 or ATG5 attenuated the cytotoxicity of Obatoclax by suppressing both autophagy and apoptosis. Finally, when apoptosis was pharmacologically inhibited, autophagic cell death was initiated in adenoid cystic carcinoma cells treated with Obatoclax.CONCLUSION:
In summary, Beclin 1 and ATG5 play important roles in regulating both Obatoclax-induced autophagy and apoptosis in adenoid cystic carcinoma.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Autofagia
/
Neoplasias das Glândulas Salivares
/
Carcinoma Adenoide Cístico
/
Proteína Beclina-1
/
Proteína 5 Relacionada à Autofagia
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Oral Dis
Assunto da revista:
ODONTOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China