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• W2073555506 abstract "Cancer progression relies on establishment of the blood supply necessary for tumor growth and ultimately metastasis. Prostate cancer mortality is primarily attributed to development of metastases rather than primary, organ-confined disease. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis in prostate tissue. Our previous studies have demonstrated that the chemopreventive bioflavonoid apigenin inhibited hypoxia-induced elevation of VEGF production at low oxygen conditions characteristic for solid tumors. Low oxygen (hypoxia) and transforming growth factor-β (TGF-β) are two major factors responsible for increased VEGF secretion. In the present study, experiments were performed to investigate the inhibitory effect of apigenin on TGF-β-induced VEGF production and the mechanisms underlying this action. Our results demonstrate that VEGF expression is induced by TGF-β1 in human prostate cancer PC3-M and LNCaP C4-2B cells, and treatment with apigenin markedly decreased VEGF production. Additionally, apigenin inhibited TGF-β1-induced phosphorylation and nuclear translocation of Smad2 and Smad3. Further experiments demonstrated that specific transient knockdown of Smad2 or Smad3 blunted apigenin's effect on VEGF expression. We also found that apigenin inhibited Src, FAK, and Akt phosphorylation in PC3-M and LNCaP C4-2B cells. Furthermore, constitutively active Src reversed the inhibitory effect of apigenin on VEGF expression and Smad2/3 phosphorylation. Taken together, our results suggest that apigenin inhibits prostate carcinogenesis by modulating TGF-β-activated pathways linked to cancer progression and metastases, in particular the Smad2/3 and Src/FAK/Akt pathways. These findings provide new insights into molecular pathways targeted by apigenin, and reveal a novel molecular mechanism underlying the antiangiogenic potential of apigenin. © 2013 Wiley Periodicals, Inc." @default.
• W2073555506 created "2016-06-24" @default.
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• W2073555506 date "2013-01-28" @default.
• W2073555506 modified "2023-10-13" @default.
• W2073555506 title "Apigenin inhibits TGF-β-induced VEGF expression in human prostate carcinoma cells via a Smad2/3- and Src-dependent mechanism" @default.
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• W2073555506 doi "https://doi.org/10.1002/mc.22005" @default.
• W2073555506 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23359392" @default.
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