title: Gallic acid, a phenolic compound, exerts anti-angiogenic effects via the PTEN/AKT/HIF-1α/VEGF signaling pathway in ovarian cancer cells.
abstract: Gallic acid (GA), a polyphenol, is widely found in numerous fruits and vegetables, particularly in hickory nuts. In the present study, we found that gallic acid, a natural phenolic compound isolated from fruits and vegetables, had a more potent growth inhibitory effect on two ovarian cancer cell lines, OVCAR-3 and A2780/CP70, than the effect on a normal ovarian cell line, IOSE-364. These results demonstrated that GA selectively inhibits the growth of cancer cells. Gene expression was examined by ELISA and western blot analysis, and gene pathways were examined by luciferase assay. It was found that GA inhibited VEGF secretion and suppressed in vitro angiogenesis in a concentration-dependent manner. GA downregulated AKT phosphorylation as well as HIF-1α expression but promoted PTEN expression. The luciferase assay results suggest that the PTEN/AKT/HIF-1α pathway accounts for the inhibitory effect of GA on VEGF expression and in vitro angiogenesis. These findings provide strong support for the high potential of GA in the prevention and therapy of ovarian cancer.
authors.affiliation: Key Laboratory for Quality Improvement of Agricultural Products of Zhejiang Province, College of Agriculture and Food Science, Zhejiang A & F University, Lin'an, Zhejiang 311300, P.R. China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Pharmaceutical Science, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Allen Y
authors.initials: AY
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Science, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
authors.affiliation: Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA.
authors.forename: Gary O
authors.initials: GO
authors.lastname: Rankin
authors.affiliation: Key Laboratory for Quality Improvement of Agricultural Products of Zhejiang Province, College of Agriculture and Food Science, Zhejiang A & F University, Lin'an, Zhejiang 311300, P.R. China.
authors.forename: Yi Charlie
authors.initials: YC
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D005707:Gallic Acid / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005707:Gallic Acid; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase