Indirubin shows anti-angiogenic activity in an in vivo zebrafish model and an in vitro HUVEC model.
OBJECTIVE
Indirubin is an active ingredient of the traditional Chinese medicine, Dang Gui Long Hui Wan, commonly used for the treatment of chronic myelocytic leukemia (CML) and other inflammatory conditions. These anti-leukemic and anti-inflammatory activities may be mediated by anti-angiogenic action. To investigate the anti-angiogenic activity of indirubin, we tested its inhibitory effect on blood vessel formation in zebrafish embryos and on endothelial cell proliferation in culture.


METHODS
The anti-angiogenic activity of indirubin was tested using transgenic zebrafish embryos with fluorescent vasculature and human umbilical vein endothelial cells (HUVECs). Apoptosis was analyzed with a terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay.


RESULTS
Indirubin dose-dependently inhibited intersegmental vessel formation in zebrafish embryos. It also inhibited HUVEC proliferation by the induction of cellular apoptosis and cell-cycle arrest at the G0/G1 phase.


CONCLUSIONS
The anti-angiogenic activity of indirubin may partly contribute to its anti-leukemic and anti-psoriatic properties and may be valuable for the treatment of diseases with excessive angiogenesis. The zebrafish model of angiogenesis was further validated in this study.
Alex
Deepa
D
Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
Lam
In Kei
IK
Lin
ZhiXiu
Z
Lee
Simon Ming Yuen
SM
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000494:pharmacology; D019684:Magnoliopsida; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology
D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D007211:Indoles; C027185:indirubin