Sub-toxic dose of apigenin sensitizes HepG2 cells to TRAIL through ERK-dependent up-regulation of TRAIL receptor DR5.
Mol Cells
; 35(1): 32-40, 2013 Jan.
Article
en En
| MEDLINE
| ID: mdl-23224239
ABSTRACT
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is regarded as a promising candidate for anticancer therapy due to its selective toxicity to cancer cells. Nevertheless, because of TRAIL resistance in some cancer cells, combined treatment with sensitizing agents is required to enhance the anticancer potential of TRAIL. In this study, we investigated the underlying mechanism of apigenin-induced sensitization of HepG2 cells to TRAIL-induced cell death. Synergistic induction of apoptosis by combination was confirmed by examining the typical morphology changes of apoptosis, PARP-cleavage, and activation of effector caspases. Z-VAD-fmk, a pan-caspase inhibitor, inhibited the enhanced cell death by combined treatment of apigenin and TRAIL, demonstrating that a caspase-dependent pathway is involved in apigenin/TRAIL-mediated apoptosis. In addition, we found that apigenin/ TRAIL co-treatment up-regulates DR5 cell surface expression. The synergistic induction of cell death by the apigenin/ TRAIL combination was significantly attenuated by DR5 blocking chimera antibody. Next, using pharmacological inhibitors, we found that ERK activation is involved in the induction of DR5 expression. Inhibition of ERK1/2 by U0126 significantly decreased the apigenin/TRAIL-induced DR5 expression and apoptosis. Taken together, our results indicate that apigenin can enhance the apoptotic effect of TRAIL via ERK-induced up-regulation of DR5.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Resistencia a Antineoplásicos
/
Proteína Quinasa 1 Activada por Mitógenos
/
Apigenina
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Proteína Quinasa 3 Activada por Mitógenos
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Ligando Inductor de Apoptosis Relacionado con TNF
/
Receptores del Ligando Inductor de Apoptosis Relacionado con TNF
Límite:
Humans
Idioma:
En
Revista:
Mol Cells
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2013
Tipo del documento:
Article
Pais de publicación:
COREA DEL SUR
/
CORÉIA DO SUL
/
KR
/
SOUTH KOREA