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Nobiletin, a polymethoxylated flavonoid from citrus, shows anti‐angiogenic activity in a zebrafish in vivo model and HUVEC in vitro model
Author(s) -
Lam Kai Heng,
Alex Deepa,
Lam In Kei,
Tsui Stephen Kwok Wing,
Yang Zi Feng,
Lee Simon Ming Yuen
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.23257
Subject(s) - nobiletin , angiogenesis , in vivo , pharmacology , chemistry , inflammation , zebrafish , umbilical vein , flavonoid , microbiology and biotechnology , biology , in vitro , biochemistry , cancer research , immunology , gene , antioxidant
Traditional Chinese medicinal herbs are a rich source of compounds with reported anti‐inflammatory and anti‐carcinogenic effects. Growing evidence shows the codependence of chronic inflammation and angiogenesis, and the potential benefits of targeting angiogenesis in the treatment of chronic inflammation and targeting inflammation in the treatment of diseases with impaired angiogenesis. We hypothesized that the anti‐inflammatory activity of the natural compounds may owe at least some of its efficacy to their anti‐angiogenic activity and hence we investigated the anti‐angiogenic activity of these compounds in vivo in zebrafish embryos and in vitro in human umbilical vein endothelial cells (HUVECs). Nobiletin, a polymethoxylated flavonoid from citrus fruits, showed anti‐angiogenic activity in both assays. Nobiletin inhibited the formation of intersegmental vessels (ISVs) in live transgenic zebrafish embryos expressing green fluorescent protein (GFP) in the vasculature. Cell cycle analysis of dissociated zebrafish embryo cells showed that nobiletin induced G0/G1 phase accumulation in a dose‐dependent manner in GFP‐positive endothelial cells. Nobiletin also dose‐dependently induced VEGF‐A mRNA expression. In HUVECs, nobiletin inhibited endothelial cell proliferation and, to a greater extent, tube formation in a dose‐dependent manner. As in the in vivo study, nobiletin induced G0/G1 cell cycle arrest in HUVECs. However, this arrest was not accompanied by an increase in apoptosis, indicating a cytostatic effect of nobiletin. This study, for the first time, identifies nobiletin as having potent anti‐angiogenic activity and suggests that nobiletin has a great potential for future research and development as a cytostatic anti‐proliferative agent. J. Cell. Biochem. 112: 3313–3321, 2011. © 2011 Wiley Periodicals, Inc.