DHMEQ, a novel NF-kappaB inhibitor, induces apoptosis and cell-cycle arrest in human hepatoma cells.
Int J Oncol
; 29(3): 713-9, 2006 Sep.
Article
em En
| MEDLINE
| ID: mdl-16865289
ABSTRACT
Several reports have indicated that nuclear factor-kappaB (NF-kappaB) is constitutively activated in a variety of cancer cells including hepatoma cells and plays a key role in their growth and survival. Dehydroxymethylepoxyquinomicin (DHMEQ) derived from the structure of an antibiotic epoxyquinomicin C is a novel NF-kappaB inhibitor. In the present study, we evaluated the effect of DHMEQ on the NF-kappaB activity in human hepatoma cells, Huh-7, HepG2 and Hep3B, and the anti-tumor effect of DHMEQ on these cells in vitro and in vivo. DHMEQ inhibited the steady-state transcriptional activity of NF-kappaB in all hepatoma cells. DHMEQ blocked the constitutive DNA-binding activity and TNF-alpha-mediated nuclear translocation of NF-kappaB in Huh-7 cells. DHMEQ (5-20 microg/ml) dose-dependently reduced the viable cell number of all hepatoma cells. DHMEQ (20 microg/ml) induced apoptosis in all hepatoma cells, especially in Hep3B cells, and cell-cycle arrest in Huh-7 and HepG2 cells. These effects were accompanied by downregulation of proteins involved in anti-apoptosis (Bcl-xL, XIAP or c-IAP2) and cell-cycle progression (cyclin D1), and induction of proteins involved in pro-apoptosis (Bax) and cell-cycle retardation (p21Waf1/Cip1), although the degree of changes by DHMEQ was different in each hepatoma cell type. Moreover, intraperitoneal administration of DHMEQ (8 mg/kg) significantly repressed the growth of Huh-7 tumor subcutaneously transplanted into BALB/c nu/nu athymic mice. Our results suggest that DHMEQ could qualify as a candidate for a new chemotherapeutic agent against human hepatoma.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzamidas
/
Ciclo Celular
/
NF-kappa B
/
Apoptose
/
Carcinoma Hepatocelular
/
Cicloexanonas
/
Neoplasias Hepáticas
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Int J Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Japão