Antiangiogenic effect of alpha-anordrin in vitro and in vivo

AIM: To study the antiangiogenic effect of alpha-anordrin (alpha-Ano), a pa rtial. antagonist of estrogen receptor. METHODS: The in vivo inhibitory eff ect of alpha-Ano on angiogenesis was determined by microvascular density (M VD) in tumors and the chicken chorioallantoic membrane (CAM) model. The in vitro effects of alpha-Ano on proliferation, migration, and attachment of h uman umbilical vein endothelial cells (HUVEC) were assessed by trypan blue exclusion, wound-induced two-dimensional migration model, and their ability to adhere to type I collagen, respectively. The possible involvement of ni tric oxide (NO) in alpha-Ano antiangiogenic effect was determined by measur ing NO content using fluorescent assay. RESULTS: alpha-Ano significantly in hibited the MVD in Lewis lung carcinoma model and this effect was correlate d with its inhibition of the tumor growth. alpha-Ano also showed an inhibit ory effect on the angiogenesis of CAM with the inhibitory rate of 53 % and such action of alpha-Ano could not be blocked by simultaneous administratio n of 17 beta-estrodiol, a typical agonist of estrogen receptor. In vitro st udies showed that alpha-ANO obviously suppressed the proliferation and migr ation of HUVEC, but had no obvious effect on the attachment of HUVEC to the type I collagen. Moreover, alpha-Ano significantly reduced the level of NO released by HUVEC in a dose- and time-dependent manner. CONCLUSION: alpha- Ano possesses an antiangiogenic effect, and this effect is mediated, at lea st in part, by reducing the NO content and subsequently inhibiting the prol iferation and migration of endothelial cells.