Department of Chemistry, University of Virginia, Charlottesville, VA 22908, USA.
Food Chem. 2013 Dec 1;141(3):1841-6. doi: 10.1016/j.foodchem.2013.05.006. Epub 2013 May 11.
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.
苯乙基异硫氰酸酯（PEITC），一种天然的饮食性异硫氰酸盐，能够抑制血管生成，但这一作用的分子机制尚不清楚。在这项研究中，我们在缺氧条件（1% O2）下，检测了 PEITC 对多种人癌细胞系细胞内缺氧诱导因子（HIF-1α）水平和细胞外血管内皮生长因子（VEGF）水平的影响。令人惊讶的是，我们观察到 PEITC 抑制了人胶质瘤 U87、人前列腺癌 DU145、结肠癌 HCT116、肝癌 HepG2 和乳腺癌 SkBr3 细胞在缺氧条件下的 HIF-1α积累。PEITC 处理还显著降低了缺氧诱导的 VEGF 分泌。在缺氧条件下用 PEITC 处理时，HIF-1α 积累的抑制与 PI3K 和 MAPK 通路有关。综上所述，这些结果表明，PEITC 通过抑制 PI3K 和 MAPK 信号通路抑制 HIF-1α 的表达，并为 PEITC 的抗癌特性提供了新的见解。
