PUBLICATION
Mechanistic study of the in vitro and in vivo inhibitory effects of protocatechuic acid and syringic acid on VEGF-induced angiogenesis
- Authors
- Hu, J., Lin, S., Huang, J.J., Cheung, P.C.K.
- ID
- ZDB-PUB-180612-1
- Date
- 2018
- Source
- Journal of Agricultural and Food Chemistry 66(26): 6742-6751 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Angiogenesis Inhibitors/administration & dosage*
- Animals
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Gallic Acid/administration & dosage
- Gallic Acid/analogs & derivatives*
- Human Umbilical Vein Endothelial Cells/cytology
- Human Umbilical Vein Endothelial Cells/drug effects
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- Hydroxybenzoates/administration & dosage*
- Neovascularization, Pathologic/drug therapy*
- Neovascularization, Pathologic/metabolism
- Neovascularization, Pathologic/physiopathology
- Signal Transduction/drug effects
- Vascular Endothelial Growth Factor A/metabolism*
- Zebrafish/embryology
- Zebrafish/metabolism
- PubMed
- 29886729 Full text @ J. Agric. Food Chem.
Citation
Hu, J., Lin, S., Huang, J.J., Cheung, P.C.K. (2018) Mechanistic study of the in vitro and in vivo inhibitory effects of protocatechuic acid and syringic acid on VEGF-induced angiogenesis. Journal of Agricultural and Food Chemistry. 66(26):6742-6751.
Abstract
The anti-angiogenic 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 μM) 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-dependant 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 sub-intestinal vessel plexus formation in Tg (fli1a:EGFP) y1-type transgenic zebrafish embryos. PA and SA down-regulated the angiogenesis-related signal transduction pathway of VEGFα-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 anti-angiogenic activities and are potential targets for the design and development of anticancer agents.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping