PMID- 15219940
OWN - NLM
STAT- MEDLINE
DCOM- 20040907
LR  - 20181130
IS  - 0304-3835 (Print)
IS  - 0304-3835 (Linking)
VI  - 211
IP  - 2
DP  - 2004 Aug 10
TI  - Artesunate reduces chicken chorioallantoic membrane neovascularisation and 
      exhibits antiangiogenic and apoptotic activity on human microvascular dermal 
      endothelial cell.
PG  - 163-73
AB  - 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.
FAU - Huan-huan, Chen
AU  - Huan-huan C
AD  - Department of Clinical Pharmacology, The First Affiliated Hospital of Medical 
      College, Zhejiang University, Hangzhou 310003, People's Republic of China. 
      pharmchenh@163.com
FAU - Li-Li, You
AU  - Li-Li Y
FAU - Shang-Bin, Li
AU  - Shang-Bin L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antimalarials)
RN  - 0 (Artemisinins)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 60W3249T9M (Artesunate)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
SB  - IM
MH  - Allantois
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Animals
MH  - Antimalarials/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Artemisia/chemistry
MH  - Artemisinins/*pharmacology
MH  - Artesunate
MH  - Cell Differentiation
MH  - Cell Division
MH  - Chick Embryo
MH  - Chorion
MH  - *DNA Damage
MH  - Dose-Response Relationship, Drug
MH  - *Neovascularization, Pathologic
MH  - Receptors, Vascular Endothelial Growth Factor/drug effects/physiology
MH  - Sesquiterpenes/*pharmacology
MH  - Vascular Endothelial Growth Factor A/physiology
EDAT- 2004/06/29 05:00
MHDA- 2004/09/08 05:00
CRDT- 2004/06/29 05:00
PHST- 2003/02/10 00:00 [received]
PHST- 2003/12/19 00:00 [revised]
PHST- 2004/03/04 00:00 [accepted]
PHST- 2004/06/29 05:00 [pubmed]
PHST- 2004/09/08 05:00 [medline]
PHST- 2004/06/29 05:00 [entrez]
AID - S0304383504002241 [pii]
AID - 10.1016/j.canlet.2004.03.014 [doi]
PST - ppublish
SO  - Cancer Lett. 2004 Aug 10;211(2):163-73. doi: 10.1016/j.canlet.2004.03.014.