[Inhibitory effects of artesunate on angiogenesis].
OBJECTIVE
To investigate the inhibitory effects of artesunate on angiogenesis.


METHODS
The in vitro anti-angiogenic effect of artesunate was tested on models of angiogenesis: proliferation, migration and tube formation of human umbilical vein endothelial (HUVE) cells; The anti-angiogenic effect in vivo was evaluated in nude mice by means of human ovarian cancer HO-8910 implantation and immunohistochemical stainings for microvessel (CD31), vascular endothelial growth factor (VEGF) and VEGF receptor KDR/flk-1.


RESULTS
Artesunate significantly inhibited angiogenesis in a concentration-dependent form in range of 0.5-50 mumol.L-1. The IC50 of artesunate for HUVE cells was (21 +/- 3) mumol.L-1. Growth of xenograft tumor was decreased and microvessel density was reduced following drug-treatment with no apparent toxicity to the animals. Artesunate also remarkably lowered VEGF expression on tumor cells and KDR/flk-1 expression on endothelial cells as well as tumor cells.


CONCLUSIONS
Artesunate was shown to inhibit angiogenesis in vitro and in vivo. These findings together with the known low toxicity of artesunate are clues that artesunate may be a promising angiogenesis inhibitor.
Chen
Huan-huan
HH
Department of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, China. chenh552@163.com
Zhou
Hui-jun
HJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D019306:Artemisia / Q000737:chemistry; D037621:Artemisinins / Q000302:isolation & purification / Q000494:pharmacology*; D000077332:Artesunate; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis*; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*
D020533:Angiogenesis Inhibitors; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2