5-Formylhonokiol exerts anti-angiogenesis activity via inactivating the ERK signaling pathway
Experimental & Molecular Medicine
;
: 146-152, 2011.
Artículo
en Inglés
| WPRIM
| ID: wpr-171914
ABSTRACT
Our previous report has demonstrated that 5-formylhonokiol (FH), a derivative of honokiol (HK), exerts more potent anti-proliferative activities than honokiol in several tumor cell lines. In present study, we first explored the antiangiogenic activities of 5-formylhonokiol on proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) for the first time in vitro. Then we investigated the in vivo antiangiogenic effect of 5-formylhonokiol on zebrafish angiogenesis model. In order to clarify the underlying molecular mechanism of 5-formylhonokiol, we investigated the signaling pathway involved in controlling the angiogenesis process by western blotting assay. Wound-healing results showed that 5-formylhonokiol significantly and dose-dependently inhibited migration of cultured human umbilical vein enthothelial cells. The invasiveness of HUVEC cells was also effectively suppressed at a low concentration of 5-formylhonokiol in the transwell assay. Further F-actin imaging revealed that inhibitory effect of 5-formylhonokiol on invasion may partly contribute to the disruption of assembling stress fiber. Tube formation assay, which is associated with endothelial cells migration, further confirmed the anti-angiogenesis effect of 5-formylhonokiol. In in vivo zebrafish angiogenesis model, we found that 5-formylhonokiol dose-dependently inhibited angiogenesis. Furthermore, western blotting showed that 5-formylhonokiol significantly down-regulated extracellular signal-regulated kinase (ERK) expression and inhibited the phosphorylation of ERK but not affecting the total protein kinase B (Akt) expression and related phosphorylation, suggesting that 5-formylhonokiol might exert anti-angiogenesis capacity via down-regulation of the ERK signal pathway. Taken together, these data suggested that 5-formylhonokiol might be a viable drug candidate in antiangiogenesis and anticancer therapies.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Venas Umbilicales
/
Cicatrización de Heridas
/
Compuestos de Bifenilo
/
Pez Cebra
/
Medicamentos Herbarios Chinos
/
Endotelio Vascular
/
Transducción de Señal
/
Movimiento Celular
/
Células Cultivadas
/
Western Blotting
Tipo de estudio:
Estudio pronóstico
Límite:
Animales
/
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2011
Tipo del documento:
Artículo
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