Inhibition of endothelial cell differentiation and proinflammatory cytokine production during angiogenesis by allyl isothiocyanate and phenyl isothiocyanate.

Angiogenesis is a crucial step in the growth and metastasis of cancers. The activation of endothelial cells and their further behavior are very critical during angiogenesis. The authors analyze the effect of allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC) on angiogenesis in an in vitro model using human umbilical vein endothelial cells (HUVECs). AITC and PITC significantly inhibited endothelial cell migration, invasion, and tube formation. (3)H-thymidine proliferation assay showed that AITC and PITC significantly inhibited the proliferation of HUVECs in vitro. The authors also studied the effect of AITC and PITC on the serum cytokine profiles of angiogenesis-induced animals and found that these compounds are highly potent in the downregulation of vascular endothelial growth factor (VEGF) and proinflammatory cytokines such as interleukin (IL)-1beta , IL-6, granulocyte macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha). Treatment with these compounds showed an elevation in the levels of IL-2 and tissue inhibitor of metalloproteinases (TIMP)-1, which are antiangiogenic factors. Moreover, studies using B16F-10 melanoma cells showed that both AITC and PITC significantly reduced VEGF mRNA expression. These findings suggest that AITC and PITC act as angiogenesis inhibitors through the downregulation of VEGF and proinflammatory cytokines such as IL-1beta, IL-6, GM-CSF, and TNF-alpha and upregulation of IL-2 and TIMP.