Original Article

Antiangiogenic effect of alpha-anordrin in vitro and in vivo

Authors: Zhong-Cai Ma, Li-Guang Lou, Zhou Zhang, Bin Xu

Abstract

"AIM:
To study the antiangiogenic effect of alpha-anordrin (alpha-Ano), a partial antagonist of estrogen receptor.
METHODS:
The in vivo inhibitory effect of alpha-Ano on angiogenesis was determined by microvascular density (MVD) in tumors and the chicken chorioallantoic membrane (CAM) model. The in vitro effects of alpha-Ano on proliferation, migration, and attachment of human 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 nitric oxide (NO) in alpha-Ano antiangiogenic effect was determined by measuring NO content using fluorescent assay.
RESULTS:
alpha-Ano significantly inhibited the MVD in Lewis lung carcinoma model and this effect was correlated with its inhibition of the tumor growth. alpha-Ano also showed an inhibitory effect on the angiogenesis of CAM with the inhibitory rate of 53% and such action of alpha-Ano could not be blocked by simultaneous administration of 17 beta-estrodiol, a typical agonist of estrogen receptor. In vitro studies showed that alpha-ANO obviously suppressed the proliferation and migration 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 least in part, by reducing the NO content and subsequently inhibiting the proliferation and migration of endothelial cells."
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