Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent and independent pathways in human ovarian cancer cells.

Abstract

Ovarian cancer is 1 of the most significant malignancies in the Western world, and the antiangiogenesis strategy has been postulated for prevention and treatment of ovarian cancers. Kaempferol is a natural flavonoid present in many fruits and vegetables. The antiangiogenesis potential of kaempferol and its underlying mechanisms were investigated in two ovarian cancer cell lines, OVCAR-3 and A2780/CP70. Kaempferol mildly inhibits cell viability but significantly reduces VEGF gene expression at mRNA and protein levels in both ovarian cancer cell lines. In chorioallantoic membranes of chicken embryos, kaempferol significantly inhibits OVCAR-3-induced angiogenesis and tumor growth. HIF-1alpha, a regulator of VEGF, is downregulated by kaempferol treatment in both ovarian cancer cell lines. Kaempferol also represses AKT phosphorylation dose dependently at 5 to 20 muM concentrations. ESRRA is a HIF-independent VEGF regulator, and it is also downregulated by kaempferol in a dose-dependent manner. Overall, this study demonstrated that kaempferol is low in cytotoxicity but inhibits angiogenesis and VEGF expression in human ovarian cancer cells through both HIF-dependent (Akt/HIF) and HIF-independent (ESRRA) pathways and deserves further studies for possible application in angio prevention and treatment of ovarian cancers.

• Authors: Haitao Luo, Gary O Rankin, Lingzhi Liu, Matthew K Daddysman, Bing-Hua Jiang, Yi Charlie Chen
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 61 Issue 4 Pg. 554-63 ( 2009) ISSN: 1532-7914 [Electronic] United States
• PMID: 19838928 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Angiogenesis Inhibitors
• ERRalpha estrogen-related receptor
• Heat-Shock Proteins
• Hypoxia-Inducible Factor 1
• Kaempferols
• PPARGC1A protein, human
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Receptors, Estrogen
• Transcription Factors
• Tumor Suppressor Protein p53
• Vascular Endothelial Growth Factors
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases

Topics

• Analysis of Variance
• Angiogenesis Inhibitors (administration & dosage, pharmacology)
• Animals
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chick Embryo
• Chorioallantoic Membrane (blood supply)
• Dose-Response Relationship, Drug
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Heat-Shock Proteins (genetics, metabolism)
• Humans
• Hypoxia-Inducible Factor 1 (genetics, metabolism)
• Kaempferols (administration & dosage, genetics, metabolism, pharmacology)
• Ovarian Neoplasms (genetics, metabolism)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptors, Estrogen (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription Factors (genetics, metabolism)
• Tumor Suppressor Protein p53 (deficiency, genetics)
• Vascular Endothelial Growth Factors (genetics, metabolism)
• Xenograft Model Antitumor Assays