title: Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro.
abstract: 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 (IC(50)) 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. IC(50) values ranged from 15.4 to 49.7 microM or from 8.5 to 32.9 microM after treatment with ART or dihydroartemisinin for 48 h, 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 microM and 2.5-50 microM, 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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacology, Zhejiang University, Zhejiang 310031, Hangzhou, PR China. chenh552@163.com
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Chen
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Fang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D000077332:Artesunate; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D037621:Artemisinins; D006131:Growth Inhibitors; D012717:Sesquiterpenes; D000077332:Artesunate; C039060:artenimol