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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 817674, 9 pages
Research Article

Subtoxic Levels of Apigenin Inhibit Expression and Secretion of VEGF by Uveal Melanoma Cells via Suppression of ERK1/2 and PI3K/Akt Pathways

1Department of Ophthalmology, Show Chwan Memorial Hospital, Changhua 500, Taiwan
2Institute of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan
3Tissue Culture Center, The New York Eye and Ear Infirmary, NY 10003, USA
4Department of Optometry, Yuan Pei University, Hsinchu 30015, Taiwan

Received 5 September 2013; Accepted 23 September 2013

Academic Editor: Shun-Fa Yang

Copyright © 2013 Shih-Chun Chao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The effects of apigenin on the expression of VEGF in uveal melanoma cells have not been reported. We studied this effect and relevant signaling pathways in two human uveal melanoma cell lines (SP6.5 and C918). ELISA assay revealed that the constitutive secretion of VEGF by uveal melanoma cells was 21-fold higher than that in normal uveal melanocytes. Apigenin at subtoxic levels (1–5 μM) significantly suppressed the secretion of VEGF in a dose- and time-dependent manner in melanoma cells. VEGF levels in the conditioned culture media from SP6.5 and C918 cell lines treated with 5 μM apigenin for 24 h reduced to 29% and 21% of those in cells not treated with apigenin, respectively. RT-PCR analysis found that apigenin also decreased the expression of VEGF mRNA in melanoma cells. ELISA study of various signal pathways showed that apigenin significantly decreased phosphorylated Akt and ERK1/2 but increased phosphorylated JNK1/2 and p38 MAPK levels in melanoma cells. PI3K/Akt or ERK1/2 inhibitors significantly decreased, but JNK1/2 and p38 MAPK inhibitors did not influence the secretion of VEGF by melanoma cells, suggesting that apigenin suppresses the secretion of VEGF mainly through the inhibition of PI3K/Akt and ERK1/2 pathways.