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Carcinogenesis Advance Access originally published online on October 27, 2006
Carcinogenesis 2007 28(4):858-864; doi:10.1093/carcin/bgl205
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Apigenin inhibits tumor angiogenesis through decreasing HIF-1{alpha} and VEGF expression

Jing Fang1, Qiong Zhou1, Ling-Zhi Liu1, Chang Xia2, Xiaowen Hu1, Xianglin Shi1 and Bing-Hua Jiang1,2,*

1 The Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences Shanghai 200031, China
2 Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University Morgantown, WV 26506, USA

*To whom correspondence should be addressed. Email: bhjiang{at}hsc.wvu.edu

Apigenin is a non-toxic dietary flavonoid with anti-tumor properties. We recently showed that apigenin-inhibited hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) expression in human ovarian cancer cells under normoxic condition. However, the effect of apigenin in angiogenesis remains to be elucidated. Angiogenesis is the formation of new blood vessels and is required for tumor growth and metastasis. In this study, we showed that apigenin-inhibited expression of HIF-1 and VEGF in different cancer cells under both normoxic and hypoxic conditions. We demonstrated that apigenin significantly inhibited tumor angiogenesis in vivo, by using both the chicken chorioallantoic membrane and Matrigel plug assays. The inhibition of tumor angiogenesis was associated with the decrease of HIF-1 and VEGF in tumor tissues. Taken together, our results show that apigenin suppresses tumor angiogenesis through HIF-1 and VEGF expression.

Abbreviations: ß-gal, ß-galactosidase; CAM, chicken chorioallantoic membrane; CHX, cycloheximide; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Hsp90, heat shock protein 90; HIF-1, hypoxia-inducible factor 1; Luc, luciferase; PI3K, phosphatidylinositol 3-kinase; VEGF, vascular endothelial growth factor.

Received June 12, 2006; revised October 13, 2006; accepted October 16, 2006.


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