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) was investigated for its effects on endothelial cell proliferation in vitro and 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 angiogenesis, we investigated the effects of the organoselenium compound on this process. Human umbilical vein endothelial cells treated with p-XSC showed concentration dependent inhibition of protein synthesis and cell viability in vitro with a TCID50 value of 6 microM. Subsequently, we studied the effects of p-XSC on experimental angiogenesis. Addition of p-XSC to three-dimensional cultures inhibited endothelial cell tube formation. Furthermore, p-XSC treatment inhibited growth factor induced angiogenesis in chick chorioallantoic membrane assays and i.p. administration of p-XSC inhibited neovascularization 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.
Schumacher
J J
JJ
Department of Pharmacology, University of Minnesota, Minneapolis 55445, USA.
Upadhyaya
P
P
Ramakrishnan
S
S
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002470:Cell Survival; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007797:Laminin / Q000378:metabolism; D016566:Organoselenium Compounds / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology
D016588:Anticarcinogenic Agents; D004338:Drug Combinations; D007797:Laminin; D016566:Organoselenium Compounds; D011509:Proteoglycans; C059485:matrigel; C074153:1,4-phenylenebis(methylene)selenocyanate; D003094:Collagen