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% O2), we examined the effect of PEITC on the intracellular level of the hypoxia inducible factor (HIF-1α) 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-1α 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-1α accumulation during treatment with PEITC in hypoxia was related to PI3K and MAPK pathways. Taken together, these results suggest that PEITC inhibits the HIF-1α expression through inhibiting the PI3K and MAPK signalling pathway and provide a new insight into a potential mechanism of the anticancer properties of PEITC.
Keywords: CHX; HIF-1α; Hypoxia; Hypoxia-inducible factor-1; MMP; PAGE; PBS; PEITC; PHD; Protein synthesis; SDS; VEGF; cyclohexmide; hypoxia-inducible factor-1; matrix metallopeptidase; pVHL; phenethyl isothiocyanate; phosphate-buffered saline; polyacrylamide gel electrophoresis; proline hydroxylase; sodium dodecyl sulphate; uPA; urokinase-type plasminogen activator; vascular endothelial growth factor; von Hippel–Lindau protein.
Published by Elsevier Ltd.