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REGULATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION BY FLAVONOIDS IN HUMAN OVARIAN CANCER CELLS
Author(s) -
Chen Yi,
Xia Chang,
Jiang Binghua
Publication year - 2007
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/fasebj.21.5.a620
Subject(s) - apigenin , resveratrol , vascular endothelial growth factor , reactive oxygen species , cancer research , chemistry , protein kinase b , pi3k/akt/mtor pathway , ovarian cancer , angiogenesis , pharmacology , apoptosis , microbiology and biotechnology , biology , cancer , biochemistry , medicine , antioxidant , flavonoid , vegf receptors
Ovarian cancer is the leading cause of death for women in Western countries. Plant flavonoids are reported as antioxidants that possess antioxidative and anticarcinogenic properties. Apigenin, resveratrol, 3‐hydroxyflavone and taxifolin are flavonoids commonly found in plant cells. Vascular endothelial growth factor (VEGF) is an important protein involved in angiogenesis and tumor formation. The expression of VEGF is activated by HIF‐1a. Reactive oxygen species (ROS) including H2O2, O2.− and OH. are generated by cellular aerobic metabolism and are induced by heavy metals, growth factors, and cytokine. Recent studies indicated that ROS are involved in the development and growth of many human cancers. In this study, we studied the effect of flavonoids on the mechanism of VEGF expression in the ovarian carcinoma cells. Our studies showed that ovarian cancer cells OVCAR‐3 and A2780/CP70 produced high levels of ROS than immortalized ovarian surface epithelium (IOSE) cells. We found that ROS were spontaneously generated by ovarian cancer cells and inhibited by resveratrol, apigenin and catalase. Flavonids inhibited VEGF and ROS production in the cells. By using RT‐PCR assay, we demonstrated that taxifolin, 3‐hydroxyflavone and apigenin down regulated the expression of VEGF in the ovarian cancer cells. Our data indicated that AKT activation was induced by H2O2 treatment, and inhibited by apigenin and resveratrol. Therefore, ROS functioned as upstream of PI3K/AKT signaling pathways and were inhibited by flavonoids, apigenin and resveratrol. This research was supported in part by grant P20 RR16477 from the National Center for Research Resources awarded to the West Virginia IDeA Network for Biomedical Research Excellence.