Caffeine effect on HIFs/VEGF pathway in human glioblastoma cells exposed to hypoxia

Caffeine represents the most used psychoactive drug in the world acting as a non-selective adenosine receptor antagonist. 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. In this work, we have investigated whether caffeine counteracts GBM progression by modulating hypoxic event. 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.