Fascaplysin, a selective CDK4 inhibitor, exhibit anti-angiogenic activity in vitro and in vivo.
OBJECTIVE
This study was to evaluate the correlation of two important strategies, namely, cell cycle proliferation arrest and anti-angiogenesis. We chose fascaplysin, a marine natural product with selective CDK4 selective inhibition activity, to study its potential anti-angiogenesis effects in vivo and in vitro.


METHODS
Chorioallantoic membrane (CAM) assay was initially used as an in vivo approach to evaluate anti-angiogenic activity of fascaplysin. In addition, human umbilical vein endothelial cell (HUVEC) line was used to further confirm the anti-angiogenic activity of fascaplysin in vitro. To explore the mechanism of anti-angiogenesis, we examined the effect of fascaplysin on vascular endothelial growth factor (VEGF) expression and secretion by hepatocarcinoma cells BeL-7402.


RESULTS
The results of CAM assay suggested fascaplysin inhibited capillary plexus formation in a dose-dependent manner and suppressed VEGF in cross section. Moreover, the in vitro assay also confirmed that fascaplysin provided selective inhibition of endothelial cells proliferation towards tumor cells in low concentration. The immunocytochemical staining and ELISA verified fascaplysin could inhibit VEGF expression and secretion by BeL-7402.


CONCLUSIONS
These findings strongly suggest that fascaplysin is a natural angiogenesis inhibitor.
Lin
Jing
J
Marine Biotechnology Laboratory, Ningbo University, Post Box 71, Ningbo , 315211, People's Republic of China.
Yan
Xiao-Jun
XJ
Chen
Hai-Min
HM
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors*; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D000644:Quaternary Ammonium Compounds; D002243:Carbolines; D007212:Indolizines
D020533:Angiogenesis Inhibitors; D051358:Cyclin-Dependent Kinase 4; D007211:Indoles; D042461:Vascular Endothelial Growth Factor A; C069346:fascaplysine; D000644:Quaternary Ammonium Compounds; D002243:Carbolines; D007212:Indolizines; C495900:CDK4 protein, human