Antiangiogenic activity of a synthetic stigmastane analog

MICHELINI, FLAVIA M; BERRA, ALEJANDRO; BUENO, CARLOS; ALCHÉ, LAURA; LOMBARDI, GABRIELA; SALES, MARIA ELENA

STEROIDS

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2016 vol. 115 p. 160 - 168

0039-128X

Angiogenesis plays a critical role in initiating and promoting several diseases, such as cancer and herpeticstromal keratitis (HSK). Herein, we studied the inhibitory effect of two synthetic stigmasterol derivativeson capillary tube-like structures and on cell migration in human umbilical vein endothelial cells(HUVEC): (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3b-bromo-5a,22,23-trihydroxystigmastan-6-one (compound 2). We also studied their effect on VEGF expressionin IL-6 stimulated macrophages and in LMM3 breast cancer cells. Furthermore, we investigated theantiangiogenic activity of the compounds on corneal neovascularization in the murine model of HSKand in an experimental model of tumor-induced angiogenesis in mice.Both compounds inhibited capillary tube-like formation, but only compound 1 restrained cell migration.Compound 1, unlike compound 2, was able to reduce VEGF expression. Only compound 1 not onlyreduced the incidence and severity of corneal neovascularization, when administered at the onset of HSK,but it also restrained the development of neovascular response induced by tumor cells in mice skin.Our results show that compound 1 inhibits angiogenesis in vitro and in vivo. Therefore, compound 1would be a promising drug in the treatment of those diseases where angiogenesis represents one ofthe main pathogenic events.