Caspase-3 activation as a key factor for HBx-transformed cell death.
Cell Prolif
; 41(5): 755-74, 2008 Oct.
Article
en En
| MEDLINE
| ID: mdl-18700866
ABSTRACT
OBJECTIVES:
Nuclear factor-kappa B (NF-kappaB) activation has been associated with the tumorigenic growth of hepatitis B virus X protein (HBx)-transformed cells. This study was aimed to find a key target for treatment of HBx-mediated cancers. MATERIALS ANDMETHODS:
NF-kappaB activation, endoplasmic reticulum-stress (ER-stress), caspase-3 activation, and cell proliferation were evaluated after Chang/HBx cells permanently expressing HBx viral protein were treated with inhibitors of NF-kappaB, proteasome and DNA topoisomerase.RESULTS:
Inhibition of NF-kappaB transcriptional activity by transient transfection with mutant plasmids encoding Akt1 and glycogen synthase kinase-3beta (GSK-3beta), or by treatment with chemical inhibitors, wortmannin and LY294002, showed little effect on the survival of Chang/HBx cells. Furthermore, IkappaBalpha (S32/36A) mutant plasmid or other NF-kappaB inhibitors, 1-pyrrolidinecarbonidithioic acid and sulphasalazine, were also shown to have little effect on the cell proliferation. By contrast, proteasome inhibitor-1 (Pro1) and MG132 enhanced the HBx-induced ER-stress response and the subsequent activation of caspase-12, -9 and -3 and reduced cell proliferation. Camptothecin (CPT), however, triggered activation of caspase-3 without induction of caspase-12, and reduced cell proliferation. In addition, CPT-induced cell death was reversed by pre-treatment with z-DEVD, a caspase-3-specific inhibitor.CONCLUSIONS:
Detailed exploitation of the regulators of caspase-3 activation could open the gate for finding an efficient target for development of anticancer therapeutics against HBx-transformed hepatocellular carcinoma.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transactivadores
/
Caspasa 3
Límite:
Humans
Idioma:
En
Revista:
Cell Prolif
Año:
2008
Tipo del documento:
Article
País de afiliación:
Corea del Sur
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM