Antiangiogenic effect of alpha-anordrin in vitro and in vivo.
OBJECTIVE
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.


CONCLUSIONS
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.
Ma
Z C
ZC
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China.
Lou
L G
LG
Zhang
Z
Z
Xu
B
B
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply; D002455:Cell Division / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D009635:Norandrostanes / Q000494:pharmacology*; D011897:Random Allocation; D014471:Umbilical Veins / Q000166:cytology
D020533:Angiogenesis Inhibitors; D009635:Norandrostanes; D009569:Nitric Oxide; C010855:anordrin