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Apigenin inhibits VEGF and HIF‐1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways
Author(s) -
Fang Jing,
Xia Chang,
Cao Zongxian,
Zheng Jenny Z.,
Reed Eddie,
Jiang Bing-Hua
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2175com
Subject(s) - apigenin , angiogenesis , pi3k/akt/mtor pathway , vascular endothelial growth factor , cancer research , protein kinase b , chemistry , hypoxia inducible factors , biology , signal transduction , microbiology and biotechnology , pharmacology , vegf receptors , flavonoid , biochemistry , gene , antioxidant
Apigenin is a nontoxic dietary flavonoid that has been shown to possess anti‐tumor properties and therefore poses special interest for the development of a novel chemopreventive and/or chemotherapeutic agent for cancer. Ovarian cancer is one of the most common causes of cancer death among women. Here we demonstrate that apigenin inhibits expression of vascular endothelial growth factor (VEGF) in human ovarian cancer cells. VEGF plays an important role in tumor angiogenesis and growth. We found that apigenin inhibited VEGF expression at the transcriptional level through expression of hypoxia‐inducible factor 1α (HIF‐1α). Apigenin inhibited expression of HIF‐1α and VEGF via the PI3K/AKT/p70S6K1 and HDM2/ p53 pathways. Apigenin inhibited tube formation in vitro by endothelial cells. These findings reveal a novel role of apigenin in inhibiting HIF‐1 and VEGF expression that is important for tumor angiogenesis and growth, identifying new signaling molecules that mediate this regulation.—Fang, J., Xia, C., Cao, Z., Zheng, J. Z., Reed, E., Jiang, B.‐H. Apigenin inhibits VEGF and HIF‐1 expression via PI3K/AKT/p70S6K1 and HDM2/ p53 pathways. FASEB J. 19, 342–353 (2005)