Metabolomics of Green-Tea Catechins on Vascular-Endothelial-Growth-Factor-Stimulated Human-Endothelial-Cell Survival

J Agric Food Chem. 2018 Dec 5;66(48):12866-12875. doi: 10.1021/acs.jafc.8b05998. Epub 2018 Nov 27.

Abstract

Neovascularization causes serious oculopathy related to upregulation of vascular-endothelial-growth factor (VEGF) causing new capillary growth via endothelial cells. Green-tea-extract (GTE) constituents possess antiangiogenesis properties. We used VEGF to induce human umbilical-vein endothelial cells (HUVECs) and applied GTE, epigallocatechin gallate (EGCG), and mixtures of different compositions of purified catechins (M1 and M2) to evaluate their efficacies of inhibition and their underlying mechanisms using cell-cycle analysis and untargeted metabolomics techniques. GTE, EGCG, M1, and M2 induced HUVEC apoptosis by 22.1 ± 2, 20.0 ± 0.7, 50.7 ± 8.5, and 69.8 ± 4.1%, respectively. GTE exerted a broad, balanced metabolomics spectrum, involving suppression of the biosynthesis of cellular building blocks and oxidative-phosphorylation metabolites as well as promotion of the biosynthesis of membrane lipids and growth factors. M2 mainly induced mechanisms associated with energy and biosynthesis suppression. Therefore, GTE exerted mechanisms involving both promotion and suppression activities, whereas purified catechins induced extensive apoptosis. GTE could be a more promising antineovascularization remedy for ocular treatment.

Keywords: HUVEC; apoptosis; catechins; green-tea extract; metabolomics; proliferation.

MeSH terms

  • Apoptosis / drug effects
  • Camellia sinensis / chemistry*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Cycle Checkpoints / drug effects
  • Cell Survival / drug effects
  • Human Umbilical Vein Endothelial Cells / chemistry
  • Human Umbilical Vein Endothelial Cells / cytology*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Membrane Lipids / biosynthesis
  • Metabolomics
  • Plant Extracts / pharmacology*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Membrane Lipids
  • Plant Extracts
  • Vascular Endothelial Growth Factor A
  • Catechin
  • epigallocatechin gallate