TRAIL restores DCA/metformin-mediated cell death in hypoxia.
Biochem Biophys Res Commun
; 478(3): 1389-95, 2016 09 23.
Article
en En
| MEDLINE
| ID: mdl-27569287
ABSTRACT
Previous studies have shown that hypoxia can reverse DCA/metformin-induced cell death in breast cancer cells. Therefore, targeting hypoxia is necessary for therapies targeting cancer metabolism. In the present study, we found that TRAIL can overcome the effect of hypoxia on the cell death induced by treatment of DCA and metformin in breast cancer cells. Unexpectedly, DR5 is upregulated in the cells treated with DCA/metformin, and sustained under hypoxia. Blocking DR5 by siRNA inhibited DCA/metformin/TRAIL-induced cell death, indicating that DR5 upregulation plays an important role in sensitizing cancer cells to TRAIL-induced cell death. Furthermore, we found that activation of JNK and c-Jun is responsible for upregulation of DR5 induced by DCA/metformin. These findings support the potential application of combining TRAIL and metabolism-targeting drugs in the treatment of cancers under hypoxia.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ácido Dicloroacético
/
Ligando Inductor de Apoptosis Relacionado con TNF
/
Metformina
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2016
Tipo del documento:
Article