Phenethyl isothiocyanate inhibits hypoxia-induced accumulation of HIF-1α and VEGF expression in human glioma cells

Phenethyl isothiocyanate (PEITC), a natural dietary isothiocyanate, inhibits angiogenesis but the molecular mechanisms that underlie this effect are not known. In this study, under hypoxic conditions (1% O-2), we examined the effect of PEITC on the intracellular level of the hypoxia inducible factor (HIF-1 alpha) and extracellular level of the vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that PEITC suppressed the HIF-1 alpha accumulation during hypoxia in human glioma U87, human prostate cancer DU145, colon cancer HCT116, liver cancer HepG2, and breast cancer SkBr3 cells. PEITC treatment also significantly reduced the hypoxia-induced secretion of VEGF. Suppression of HIF-1 alpha accumulation during treatment with PEITC in hypoxia was related to PI3K and MAPK pathways. Taken together, these results suggest that PEITC inhibits the HIF-1 alpha expression through inhibiting the PI3K and MAPK signalling pathway and provide a new insight into a potential mechanism of the anticancer properties of PEITC. Published by Elsevier Ltd.