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Anticancer Agents Med Chem. 2018;18(10):1432-1439. doi: 10.2174/1871520618666180209151750.

Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia.

Author information

1
Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
2
Department of Human Science and Promotion of Quality of Life, the San Raffaele Open University of Rome, Rome, Italy.
3
Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
4
Department of Medical and Surgical Sciences and Advanced Technologies, Anatomic Pathology Section, School of Medicine, University of Catania, Catania, Italy.
5
Institute of Neurological Sciences, National Research Council, Catania, Italy.

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.

KEYWORDS:

Caffeine; MAPK/ERK; PI3K/Akt; glioblastoma multiforme; hypoxia-inducible factors; vascular endothelium growth factor.

[Indexed for MEDLINE]

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