Journal of Biotechnology & Biomaterials
Open Access

Abstract

Angiogenesis plays a critical role in initiating and promoting several diseases such as cancer and herpes stromal keratitis (HSK). Herein, we studied the inhibitory effect of two synthetic stigmasterol derivatives (22S,23S)-22,23-dihydroxystigmast-4- en-3-one (compound 1) and (22S,23S) 3���²-bromo-5���±,22,23-trihidroxistigmastan-6-ona (compound 2) on capillary tube-like structures and cell migration in human umbilical vein endothelial cells (HUVEC). We also studied their effect on VEGF expression in IL-6 stimulated macrophages and in LMM3 breast cancer cells. Furthermore, we investigated the anti-angiogenic activity of the compounds on corneal neovascularization in the murine model of HSK and in an experimental model of tumor induced angiogenesis in mice. Both compounds were able to inhibit capillary tube-like formation but only compound 1 restrained cell migration. Also only compound 1 reduced the incidence and severity of corneal neovascularization when it was administered at the onset of HSK and was able to inhibit 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. This property would not be a consequence of its anti-inflammatory activity already reported since other synthetic molecules belonging to the same family exhibited anti-inflammatory activity but did not behave as anti-angiogenic compounds. Hence, it would be a promising drug for the treatment of those diseases in which angiogenesis represents one of the main pathogenic events.

Biography

Email: lalche@qb.fcen.uba.ar