Inhibition of vascular endothelial cells by 1,4-phenylenebis (methylene)selenocyanate - A novel chemopreventive organoselenium compound

Organoselenium compound 1,4-phenylenebis(methylene)selenocyanate (p-XSC) wa s investigated for its effects on endothelial cell proliferation in vitro a nd angiogenesis in vivo. The organoselenium compound, p-XSC, has been shown to prevent carcinogen- induced tumorigenesis in murine model systems with low toxicity. Since tumor growth and metastasis are dependent on angiogenes is, we investigated the effects of the organoselenium compound on this proc ess. Human umbilical vein endothelial cells treated with p-XSC showed conce ntration dependent inhibition of protein synthesis and cell viability in vi tro with a TCID50 value of 6 muM. Subsequently, we studied the effects of p -XSC on experimental angiogenesis. Addition of p-XSC to three-dimensional c ultures inhibited endothelial cell tube formation. Furthermore, p-XSC treat ment inhibited growth factor induced angiogenesis in chick chorioallantoic membrane assays and i.p. administration of p-XSC inhibited neovascularizati on induced by tumor cells implanted subcutaneously into athymic mice. These studies suggest that vascular endothelium is an additional target for the chemopreventive organoselenium compound p-XSC.