AICAR activates ER stress-dependent apoptosis in gallbladder cancer cells.
Biochem Biophys Res Commun
; 482(2): 246-252, 2017 Jan 08.
Article
en En
| MEDLINE
| ID: mdl-27847321
ABSTRACT
AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, its activity in human gallbladder cancer cells was evaluated here. We show that AICAR provoked significant apoptosis in human gallbladder cancer cell lines (Mz-ChA-1, QBC939 and GBC-SD) and primary gallbladder cancer cells. AICAR-induced cytotoxicity in gallbladder cancer cells appears independent of AMPK activation. Inhibition of AMPK, via AMPKα shRNA knockdown or dominant negative mutation (T172A), failed to rescue GBC-SD cells from AICAR. Further, forced-activation of AMPK, by adding two other AMPK activators (A769662 and Compound 13), or expressing a constitutively-active mutant AMPKα (T172D), didn't induce GBC-SD cell death. Remarkably, AICAR treatment in gallbladder cancer cells induced endoplasmic reticulum (ER) stress activation, the latter was tested by caspase-12 activation, C/EBP homologous protein (CHOP) expression and IRE1/PERK phosphorylation. Contrarily, salubrinal (the ER stress inhibitor), z-ATAD-fmk (the caspase-12 inhibitor) or CHOP shRNAs significantly attenuated AICAR-induced gallbladder cancer cell apoptosis. Together, we conclude that AICAR-induced gallbladder cancer cell apoptosis requires ER stress activation, but is independent of AMPK.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ribonucleótidos
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Apoptosis
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Proteínas Quinasas Activadas por AMP
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Estrés del Retículo Endoplásmico
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Neoplasias de la Vesícula Biliar
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Aminoimidazol Carboxamida
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article