Artesunate reduces chicken chorioallantoic membrane neovascularisation and exhibits antiangiogenic and apoptotic activity on human microvascular dermal endothelial cell.
Artesunate (ART), a semi-synthetic derivative of artemisinin extracted from the Chinese herb Artemisia annua, is a safe and effective antimalarial drug. ART has now been analyzed for its anti-angiogenic activity in vivo and in vitro. The anti-angiogenic effect in vivo was evaluated on chicken chorioallantoic membrane (CAM) neovascularisation model. ART started to significantly inhibit CAM angiogenesis at a low concentration of 10 nm/100 microl/egg, and completely inhibited the angiogenesis at 80 nm/100 microl/egg. The inhibitory effect of in vitro angiogenesis was tested on the models of proliferation and differentiation of human microvascular dermal endothelial cell line, an important representive of endothelial cells, as well as immunocytochemistry assay for two major VEGF receptors (Flt-1 and KDR/flk-1) expressions. The results showed that ART could remarkably inhibit proliferation and differentiation of endothelial cells in a dose-dependent form in a range of 12.5-100 microM. ART also could reduce Flt-1 and KDR/flk-1 expressions in a range of 0.1-0.5 microM. Furthermore, we examined the apoptosis of human microvascular dermal endothelial cell line induced by ART. The apoptosis was detected by morphological assay of ethidium bromide (EB)/acridine orange (AO) dual staining as well as DNA fragmentation assay of TUNEL labeling and quantified by flowcytometric PI assay. Our results suggest that the antiangiogenic effect induced by ART might occur by the induction of cellular apoptosis. These findings and the known low toxicity indicated ART might be a promising candidate for angiogenesis inhibitors.
Huan-huan
Chen
C
Department of Clinical Pharmacology, The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310003, People's Republic of China. pharmchenh@163.com
Li-Li
You
Y
Shang-Bin
Li
L
D000482:Allantois; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019306:Artemisia / Q000737:chemistry; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002454:Cell Differentiation; D002455:Cell Division; D002642:Chick Embryo; D002823:Chorion; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D009389:Neovascularization, Pathologic; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects / Q000502:physiology; D012717:Sesquiterpenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D020533:Angiogenesis Inhibitors; D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D000077332:Artesunate; D040262:Receptors, Vascular Endothelial Growth Factor