Mechanistic Study of the In Vitro and In Vivo Inhibitory Effects of Protocatechuic Acid and Syringic Acid on VEGF-Induced Angiogenesis
Publication in refereed journal

香港中文大學研究人員
替代計量分析
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摘要The antiangiogenic activities of two structurally similar phenolics, protocatechuic acid (PA) and syringic acid (SA), were investigated. In vitro study using HUVECs demonstrated that both PA and SA (at 25 mu M) significantly (p < 0.05) inhibited VEGF-induced cell proliferation by 22.68 +/- 5.6% and 21.93 +/- 2.0%, respectively; cell migration by 50.04 +/- 3.3% and 39.72 +/- 4.7%, respectively; cell invasion by 44.16 +/- 4.23% and 51.90 +/- 2.73%, respectively; and cellular ROS generation by 11.48 +/- 6.32% and 21.17 +/- 9.10%, respectively. Our mechanistic study revealed that PA and SA blocked the VEGFR2-dependent Akt/MMP2 and ERK pathways in HUVECs. These inhibitory effects were further confirmed by a decrease of endogenous alkaline phosphatase activity for PA and SA (21.47 +/- 1.77% and 10.37 +/- 1.27%, respectively) and the suppression of subintestinal vessel plexus formation in Tg (flila:EGFP) y1-type transgenic zebrafish embryos. PA and SA down-regulated the angiogenesis-related signal transduction pathway of VEGF alpha-VEGFR2 or Ang2-Tie2 in zebrafish. Moreover, it was also found that PA demonstrated a better inhibition on VEGF-induced migration of HUVEC and zebrafish vasculature. This might be due to the different number of hydroxyl and methoxy substituents possessed by PA and SA. Taken together, these findings indicate that phenolics PA and SA have potent antiangiogenic activities and are potential targets for the design and development of anticancer agents.
出版社接受日期10.06.2018
著者Jiamiao Hu, Shaoling Lin, Jim Junhui Huan, Peter C. K. Cheung
期刊名稱Journal of Agricultural and Food Chemistry
出版年份2018
月份7
日期5
卷號66
出版社American Chemical Society
頁次6742 - 6751
國際標準期刊號0021-8561
電子國際標準期刊號1520-5118
語言美式英語
關鍵詞angiogenesis, protocatechuic acid, syringic acid, HUVECs, VEGF

上次更新時間 2020-16-09 於 03:28