Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis and invasion in vitro

Biomed Pharmacother. 2017 Jun;90:713-723. doi: 10.1016/j.biopha.2017.04.022. Epub 2017 Apr 15.

Abstract

Patients with glioblastoma multiforme (GBM) that are cancer stem-cell-positive (GSC [+]) essentially cannot benefit from anti-angiogenic or anti-invasive therapy. In the present study, the potential anti-angiogenic and anti-invasive effects of Olea europaea (olive) leaf extract (OLE) were tested using GSC (+) tumours. OLE (2mg/mL) caused a significant reduction in tumour weight, vascularisation, invasiveness and migration (p=0.0001, p<0.001, p=0.004; respectively) that was associated with reducing the expression of VEGFA, MMP-2 and MMP-9. This effect was synergistically increased in combination with bevacizumab. Therefore, our current findings may contribute to research on drugs that inhibit the invasiveness of GBM.

Keywords: Angiogenesis; Glioblastoma cancer stem cell; Invasion; MMP2; MMP9; Olea europaea leaf extract; VEGFA.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Bevacizumab / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Drug Synergism
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness / pathology
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Olea / chemistry*
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Plant Extracts
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9