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Indirubin‐3'‐monoxime, a derivative of a chinese antileukemia medicine, inhibits angiogenesis
Author(s) -
Kim JinKyung,
Shin Eun Kyung,
Kang YoungHee,
Park Jung Han Yoon
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23055
Subject(s) - matrigel , angiogenesis , umbilical vein , indirubin , chemistry , microbiology and biotechnology , zebrafish , cancer research , pharmacology , in vitro , biochemistry , medicine , biology , indigo , art , visual arts , gene
Although the antiangiogenic activity of indirubin‐3‐monoxime (I3M), a derivative of a Chinese anti‐leukemia medicine, has been demonstrated using transgenic zebrafish, the detail molecular mechanism has not been elicited. To further establish its role in antiangiogenic activity, we tested its potential against human umbilical vein endothelial cells (HUVECs) and the in vivo Matrigel plug model was applied to evaluate new vessel formation. We also investigated the molecular mechanisms of I3M‐induced antiangiogenic effects in HUVECs. We found that I3M significantly inhibited HUVEC proliferation (2.5–20 µM), migration (2.5–20 µM), and tube formation (10–20 µM) in HUVECs. The number of microvessels growing from the aortic rings was suppressed by I3M treatment. Moreover, I3M suppressed neovascularization in Matrigel plugs in mice. The underlying antiangiogenic mechanism of I3M was correlated with down‐regulation of the vascular endothelial growth factor receptor‐2 activation, at least a part. These findings emphasize the potential use of I3M in pathological situations involving stimulated angiogenesis, such as tumor development. J. Cell. Biochem. 112: 1384–1391, 2011. © 2011 Wiley‐Liss, Inc.