Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo.
Previous studies, including those from our laboratory, have revealed that phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous vegetables, not only affords significant protection against chemically induced cancer in animal models but also inhibits growth of cancer cells in culture and in vivo by causing cell cycle arrest and apoptosis induction. We now report a novel response to PEITC involving inhibition of angiogenesis in vitro and ex vivo at pharmacologically achievable concentrations. The PEITC treatment caused a decrease in survival of human umbilical vein endothelial cells (HUVEC) in a concentration- and time-dependent manner. The capillary-like tube structure formation (in vitro neovascularization) and migration (invasion potential) by HUVEC was also inhibited significantly in the presence of PEITC at pharmacologically relevant concentrations (<1 mumol/L). The PEITC-mediated inhibition of angiogenic features of HUVEC in vitro was associated with suppression of vascular endothelial growth factor (VEGF) secretion, down-regulation of VEGF receptor 2 protein levels, and inactivation of prosurvival serine-threonine kinase Akt. The PEITC treatment reduced migration by PC-3 human prostate cancer cells, which correlated with inactivation of Akt and suppression of VEGF, epidermal growth factor (EGF), and granulocyte colony-stimulating factor (G-CSF) secretion. The PEITC-mediated inhibition of PC-3 cell migration was statistically significantly attenuated by ectopic expression of constitutively active Akt. Most importantly, PEITC treatment inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay. In conclusion, the present study suggests that inhibition of angiogenesis may be an important mechanism in cancer chemoprevention by PEITC.
Xiao
Dong
D
Department of Pharmacology and University Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
Singh
Shivendra V
SV
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology / Q000627:therapeutic use*; D008954:Models, Biological; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D042461:Vascular Endothelial Growth Factor A; C058305:phenethyl isothiocyanate; D040262:Receptors, Vascular Endothelial Growth Factor