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Research ArticleArticle

9-β-d-Arabinofuranosyl-2-fluoroadenine Inhibits Expression of Vascular Endothelial Growth Factor through Hypoxia-Inducible Factor-1 in Human Ovarian Cancer Cells

Jing Fang, Zongxian Cao, Yi Charlie Chen, Eddie Reed and Bing-Hua Jiang
Molecular Pharmacology July 2004, 66 (1) 178-186; DOI: https://doi.org/10.1124/mol.66.1.178
Jing Fang
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Zongxian Cao
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Yi Charlie Chen
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Eddie Reed
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Bing-Hua Jiang
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Abstract

Ovarian cancer is the leading cause of death from gynecological malignancy and has the worst prognosis of all gynecological cancers. Vascular endothelial growth factor (VEGF) plays an important role in ovarian cancer development. 9-β-d-Arabinofuranosyl-2-fluoroadenine (Fara-A), a nucleotide analog, is frequently used in treating certain types of cancer. However, the effectiveness of Fara-A on ovarian cancer cells is unknown. In this study, we found that Fara-A inhibited VEGF expression in human ovarian cancer cells. Fara-A inhibited VEGF transcriptional activation through hypoxia-inducible factor 1 (HIF-1). HIF-1 is composed of HIF-1α and -1β subunits. Fara-A inhibited expression of HIF-1α but not HIF-1β. Overexpression of HIF-1α reversed Fara-A-inhibited VEGF transcriptional activation. Our results demonstrated that Fara-A inhibited VEGF transcriptional activation through HIF-1α expression. Fara-A partly inhibited HIF-1α mRNA levels. Fara-A blocked the activation of AKT but not of ERK1/2. Overexpression of AKT reversed the Fara-A-inhibited VEGF transcriptional activation, suggesting that Fara-A inhibits VEGF expression via phosphatidylinositol 3-kinase/AKT signaling. These results demonstrate a new function of Fara-A in inhibiting VEGF and HIF-1α expression and identify a potential molecular mechanism of the regulation.

  • Received December 10, 2003.
  • Accepted April 20, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 66 (1)
Molecular Pharmacology
Vol. 66, Issue 1
1 Jul 2004
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Research ArticleArticle

9-β-d-Arabinofuranosyl-2-fluoroadenine Inhibits Expression of Vascular Endothelial Growth Factor through Hypoxia-Inducible Factor-1 in Human Ovarian Cancer Cells

Jing Fang, Zongxian Cao, Yi Charlie Chen, Eddie Reed and Bing-Hua Jiang
Molecular Pharmacology July 1, 2004, 66 (1) 178-186; DOI: https://doi.org/10.1124/mol.66.1.178

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Research ArticleArticle

9-β-d-Arabinofuranosyl-2-fluoroadenine Inhibits Expression of Vascular Endothelial Growth Factor through Hypoxia-Inducible Factor-1 in Human Ovarian Cancer Cells

Jing Fang, Zongxian Cao, Yi Charlie Chen, Eddie Reed and Bing-Hua Jiang
Molecular Pharmacology July 1, 2004, 66 (1) 178-186; DOI: https://doi.org/10.1124/mol.66.1.178
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