Brassinosteroids inhibit in vitro angiogenesis in human endothelial cells

• Published in: Steroids 2012-11, Vol.77 (13), p.1502-1509
• Main Authors: Rárová, Lucie, Zahler, Stefan, Liebl, Johanna, Kryštof, Vladimír, Sedlák, David, Bartůněk, Petr, Kohout, Ladislav, Strnad, Miroslav
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - metabolism; Angiogenesis Inhibitors - pharmacology; Biological and medical sciences; Brassinosteroids - metabolism; Brassinosteroids - pharmacology; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - metabolism; Fundamental and applied biological sciences. Psychology; Human umbilical vein endothelial cells; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Migration; Natural products; Neovascularization, Physiologic - drug effects; Receptors; Vertebrates: endocrinology
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2012.08.011

[Display omitted] ► First evidence of brassinosteroids’ activities in endothelial cells. ► Antiangiogenic properties of natural brassinosteroids and their derivative in vitro. ► 24-Epibrassinolide, 28-homocastasterone and cholestanon are active compounds. ► Cholestanon activate estrogen receptors and androgen receptor. Antiangiogenic activity of the brassinosteroid plant hormones (BRs) and their derivative cholestanon was investigated in human umbilical vein endothelial cells (HUVEC) and in human microvascular endothelial cells (HMEC-1). 24-Epibrassinolide and 28-homocastasterone from group of 21 tested natural BRs inhibited migration of HUVEC cells. Seven tested BRs decreased the number of tubes significantly. Synthetic analogue cholestanon inhibited angiogenesis in vitro more effectively than natural BRs. Because of the similarity of BRs to human steroids, we have also studied interactions of BRs with human steroid receptors. Synthetic BRs cholestanon showed agonistic effects on estrogen-receptor-α, estrogen-receptor-β and androgen receptor. Of the natural BRs, 24-epibrassinolide was found to be a weak antagonist of estrogen-receptor-α (ERα). Our results provide the first evidence that large group of BRs can inhibit in vitro angiogenesis of primary endothelial cells. BRs constitute a novel group of human steroid receptor activators or inhibitors with capacity to inhibit angiogenesis.