Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro

被引:230
作者
Chen, HH [1 ]
Zhou, HJ [1 ]
Fan, X [1 ]
机构
[1] Zhejiang Univ, Coll Pharmacol, Dept Pharmacol & Toxicol, Zhengzhou 310031, Peoples R China
关键词
artesunate; dihydroartemisinin; tumor; angiogenesis; tube formation;
D O I
10.1016/S1043-6618(03)00107-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Artemisinin derivatives artesunate (ART) and dihydroartemisinin are remarkable anti-malarial drugs with low toxicity to humans. In the present investigation, we find they also inhibited tumor cell growth and suppressed angiogenesis in vitro. The anti-cancer activity was demonstrated by inhibition (IC50) of four human cancer cell lines: cervical cancer Hela, uterus chorion cancer JAR, embryo transversal cancer RD and ovarian cancer HO-8910 cell lines growth by the MTT assay. IC50 values ranged from 15.4 to 49.7 muM or from 8.5 to 32.9 muM after treatment with ART or dihydroartemisinin for 48 It, indicating that dihydroartemisinin was more effective than ART in inhibiting cancer cell lines. The anti-angiogenic activities were tested on in vitro models of angiogenesis, namely, proliferation, migration and tube formation of human umbilical vein endothelial (HUVE) cells. We investigated the inhibitory effects of ART and dihydroartemisinin on HUVE cells proliferation by cell counting, migration into the scratch wounded area in HUVE cell monolayers and microvessel tube-like formation on collagen gel. The results showed ART and dihydroartemisinin significantly inhibited angiogenisis in a dose-dependent form in range of 12.5-50 muM and 2.5-50 muM, respectively. They indicated that dihydroartemisinin was more effective than ART in inhibiting angiogenesis either. These results and the known low toxicity are clues that ART and dihydroartemisinin may be promising novel candidates for cancer chemotherapy. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:231 / 236
页数:6
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