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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
Lam K.H.1; Alex D.1; Lam I.K.1; Tsui S.K.W.2; Yang Z.F.3; Lee S.M.Y.1
2011
Source PublicationJournal of Cellular Biochemistry
ISSN7302312
Volume112Issue:11Pages:3313
Abstract

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. © 2011 Wiley Periodicals, Inc.

KeywordAngiogenesis Anti-inflammatory Cell Cycle Flavonoid Nobiletin Zebrafish
DOI10.1002/jcb.23257
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000296423000026
The Source to ArticleScopus
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Cited Times [WOS]:40   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLee S.M.Y.
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Av. Padre Tomás Pereira S.J., Taipa, Macao SAR, China
2.School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
3.Guangzhou Institute of Respiratory Diseases, State Key Laboratory of Respiratory Disease (Guangzhou Medical College), The First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510230, Guangdong Province, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Lam K.H.,Alex D.,Lam I.K.,et al. Nobiletin, a polymethoxylated flavonoid from citrus, shows anti-angiogenic activity in a zebrafish in vivo model and HUVEC in vitro model[J]. Journal of Cellular Biochemistry,2011,112(11):3313.
APA Lam K.H.,Alex D.,Lam I.K.,Tsui S.K.W.,Yang Z.F.,&Lee S.M.Y..(2011).Nobiletin, a polymethoxylated flavonoid from citrus, shows anti-angiogenic activity in a zebrafish in vivo model and HUVEC in vitro model.Journal of Cellular Biochemistry,112(11),3313.
MLA Lam K.H.,et al."Nobiletin, a polymethoxylated flavonoid from citrus, shows anti-angiogenic activity in a zebrafish in vivo model and HUVEC in vitro model".Journal of Cellular Biochemistry 112.11(2011):3313.
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