Two novel chiral tetranucleate copper-based complexes: crystal structures, nanoparticles, and inhibiting angiogenesis and the growth of human breast cancer by regulating the VEGF/VEGFR2 signal pathway in vitro

Dalton Trans. 2020 May 14;49(18):6043-6055. doi: 10.1039/d0dt00380h. Epub 2020 Apr 22.

Abstract

The single crystals of two novel copper(ii)-based complexes containing l-methioninol-derived Schiff bases were obtained and characterized. The nanoparticles of these complexes were prepared and their cellular uptake was measured in MDA-MB-231 cells and HUVECs. It was found that these complexes could remarkably induce apoptosis, inhibit proliferation, suppress migration and metastasis, and inhibit angiogenesis and the growth of triple-negative breast cancer derived from MDA-MB-231 cells in vitro. Meanwhile, these complexes exhibit anticancer and antiangiogenic functions by activating the important protein molecules VEGFR2, FAK, AKT and Erk1/2 or their phosphorylated molecules p-VEGFR2, p-FAK, p-AKT, and p-Erk1/2 in the VEGF/VEGFR2 signaling pathway, collapsing the mitochondrial membrane potential, and damaging the level of reactive oxygen species.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Copper / chemistry
  • Copper / pharmacology*
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Particle Size
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Signal Transduction / drug effects
  • Surface Properties
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Protein Kinase Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Copper
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2