Blockade of TNF-α-induced NF-κB signaling pathway and anti-cancer therapeutic response of dihydrotanshinone I.
Int Immunopharmacol
; 28(1): 764-72, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26283590
The nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, apoptosis, and angiogenesis. We identified dihydrotanshinone I as an inhibitor of NF-κB activation through our research on Salvia miltiorrhiza Bunge. In this study, we found that dihydrotanshinone I significantly inhibited the expression of NF-κB reporter gene induced by TNF-α in a dose-dependent manner. And dihydrotanshinone I also inhibited TNF-α induced phosphorylation and degradation of IκBα, phosphorylation and nuclear translocation of p65. Furthermore, pretreatment of cells with this compound prevented the TNF-α-induced expression of NF-κB target genes, such as anti-apoptosis (cIAP-1 and FLIP), proliferation (COX-2), invasion (MMP-9), angiogenesis (VEGF), and major inflammatory cytokines (TNF-α, IL-6, and MCP1). We also demonstrated that dihydrotanshinone I potentiated TNF-α-induced apoptosis. Moreover, dihydrotanshinone I significantly impaired activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and stress-activated protein kinase/c-Jun NH2-terminal kinase (JNK/SAPK). In vivo studies demonstrated that dihydrotanshinone I suppressed the growth of HeLa cells in a xenograft tumor model, which could be correlated with its modulation of TNF-α production. Taken together, dihydrotanshinone I could be a valuable candidate for the intervention of NF-κB-dependent pathological conditions such as inflammation and cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenantrenos
/
Expresión Génica
/
FN-kappa B
/
Factor de Necrosis Tumoral alfa
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos