title: Phenethyl isothiocyanate inhibits hypoxia-induced accumulation of HIF-1α and VEGF expression in human glioma cells.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Brinda
authors.initials: B
authors.lastname: Gupta
authors.forename: Linda
authors.initials: L
authors.lastname: Chiang
authors.forename: KyungMin
authors.initials: K
authors.lastname: Chae
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017879:Isothiocyanates; D042461:Vascular Endothelial Growth Factor A; C058305:phenethyl isothiocyanate
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