Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia.
Anticancer Agents Med Chem
; 18(10): 1432-1439, 2018.
Article
em En
| MEDLINE
| ID: mdl-29424319
ABSTRACT
BACKGROUND:
Caffeine represents the most used psychoactive drug in the world acting through different mechanisms of action and on several molecular targets. It exerts an anti-cancer role in glioblastoma multiforme (GBM). This neoplasia is characterized by extensive hypoxic foci triggering hypoxia-inducible factors (HIFs) expression. Among these factors, HIF-1α performs a crucial role in the induction of vascular endothelium growth factor (VEGF), a key player in angiogenesis and cell migration.METHODS:
In this work, we have investigated whether caffeine counteracts GBM progression by modulating hypoxic event. Moreover, we analyzed the activation of phosphoinositide three kinase (PI3K)/Akt and mammalian mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling cascades.RESULTS:
Our results have indicated that this psychostimulant drug significantly reduced HIF-1α and VEGF expression in GBM cells exposed to hypoxia. This effect is mediated through inhibition of PI3K/Akt and MAPK/ERK signaling pathways both implied in HIFs regulation.CONCLUSION:
The present data give new insight into antitumor activity of caffeine during GBM progression.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cafeína
/
Glioblastoma
/
Fatores de Crescimento do Endotélio Vascular
/
Inibidores de Proteínas Quinases
/
Fatores de Transcrição Hélice-Alça-Hélice Básicos
/
Hipóxia
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article