Ascofuranone suppresses EGF-induced HIF-1α protein synthesis by inhibition of the Akt/mTOR/p70S6K pathway in MDA-MB-231 breast cancer cells.
Toxicol Appl Pharmacol
; 273(3): 542-50, 2013 Dec 15.
Article
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| MEDLINE
| ID: mdl-24096035
ABSTRACT
Hypoxia-inducible factor (HIF)-1 plays an important role in tumor progression, angiogenesis and metastasis. In this study, we investigated the potential molecular mechanisms underlying the anti-angiogenic effect of ascofuranone, an isoprenoid antibiotic from Ascochyta viciae, in epidermal growth factor (EGF)-1 responsive human breast cancer cells. Ascofuranone significantly and selectively suppressed EGF-induced HIF-1α protein accumulation, whereas it did not affect the expression of HIF-1ß. Furthermore, ascofuranone inhibited the transcriptional activation of vascular endothelial growth factor (VEGF) by reducing protein HIF-1α. Mechanistically, we found that the inhibitory effects of ascofuranone on HIF-1α protein expression are associated with the inhibition of synthesis HIF-1α through an EGF-dependent mechanism. In addition, ascofuranone suppressed EGF-induced phosphorylation of Akt/mTOR/p70S6 kinase, but the phosphorylation of ERK/JNK/p38 kinase was not affected by ascofuranone. These results suggest that ascofuranone suppresses EGF-induced HIF-1α protein translation through the inhibition of Akt/mTOR/p70S6 kinase signaling pathways and plays a novel role in the anti-angiogenic action.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sesquiterpenos
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Transducción de Señal
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Inhibidores de la Angiogénesis
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Factor A de Crecimiento Endotelial Vascular
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Factor de Crecimiento Epidérmico
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Subunidad alfa del Factor 1 Inducible por Hipoxia
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Año:
2013
Tipo del documento:
Article