MDL-12330A potentiates TRAIL-induced apoptosis in gastric cancer cells through CHOP-mediated DR5 upregulation
The Korean Journal of Physiology and Pharmacology
; : 397-405, 2017.
Article
en En
| WPRIM
| ID: wpr-727976
Biblioteca responsable:
WPRO
ABSTRACT
MDL-12330A is a widely used adenylyl cyclase (AC) inhibitor that blocks AC/cAMP signaling. In this study, we demonstrated a novel antitumor activity of this drug in gastric carcinoma (GC) cell lines. In these GC cells, MDL-12330A reduced cell viability and induced cell death in a concentration-dependent manner. At a moderate concentration (~20 µM), MDL-12330A mainly induced apoptotic death whereas at concentrations greater than 20 µM, it increased non-apoptotic cell death. The induction of apoptosis was at least partially regulated by CHOP-mediated DR5 upregulation, as detected by immunoblotting and gene interference assays. More importantly, low concentrations of MDL-12330A effectively enhanced recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (rhTRAIL)-induced apoptosis and clonogenicity in these gastric cancer cells. This study demonstrates a possible role of MDL-12330A as a potential sensitizer to TRAIL, and suggests a novel therapeutic strategy targeting gastric cancer cells.
Palabras clave
Texto completo:
1
Índice:
WPRIM
Asunto principal:
Neoplasias Gástricas
/
Immunoblotting
/
Regulación hacia Arriba
/
Línea Celular
/
Supervivencia Celular
/
Adenilil Ciclasas
/
Factor de Necrosis Tumoral alfa
/
Muerte Celular
/
Apoptosis
Límite:
Humans
Idioma:
En
Revista:
The Korean Journal of Physiology and Pharmacology
Año:
2017
Tipo del documento:
Article