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

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

Volume: 18 Issue: 10

Author(s): Grazia Maugeri, Agata G. D'Amico, Daniela M. Rasà, Salvatore Saccone, Concetta Federico, Gaetano Magro, Sebastiano Cavallaro and Velia D'Agata*

Affiliation:

• Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania,Italy

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

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.

Cite this article as:

Maugeri Grazia, D'Amico G. Agata, Rasà M. Daniela, Saccone Salvatore , Federico Concetta , Magro Gaetano , Cavallaro Sebastiano and D'Agata Velia *, Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (10) . https://dx.doi.org/10.2174/1871520618666180209151750