Curcumin enhances TRAIL-induced apoptosis of breast cancer cells by regulating apoptosis-related proteins.
Mol Cell Biochem
; 383(1-2): 39-48, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23846485
ABSTRACT
The TNF-related apoptosis inducing ligand (TRAIL) has promising anti-cancer therapeutic activity, although significant percentage of primary tumors resistant to TRAIL-induced apoptosis remains an obstacle to the extensive use of TRAIL-based mono-therapies. Natural compound curcumin could potentially sensitize resistant cancer cells to TRAIL. We found that the combination of TRAIL with curcumin can synergistically induces apoptosis in three TRAIL-resistant breast cancer cell lines. The mechanism behind this synergistic cell death was investigated by examining an effect of curcumin on the expression and activation of TRAIL-associated cell death proteins. Immunoblotting, RNA interference, and use of chemical inhibitors of TRAIL-activate signaling revealed differential effects of curcumin on the expression of Mcl-1 and activities of ERK and Akt. Curcumin-induced production of reactive oxygen species did not affect total expression of DR5 but it enhanced mobilization of DR5 to the plasma membrane. In these breast cancer cells curcumin also induced downregulation of IAP proteins. Taken together, our data suggest that a combination of TRAIL and curcumin is a potentially promising treatment for breast cancer, although the specific mechanisms involved in this sensitization could differ even among breast cancer cells of different origins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Apoptose
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Curcumina
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Proteínas Reguladoras de Apoptose
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Ligante Indutor de Apoptose Relacionado a TNF
Limite:
Female
/
Humans
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2013
Tipo de documento:
Article