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

• Published in: Biomedicine & pharmacotherapy 2017-06, Vol.90, p.713-723
• Main Authors: Tezcan, Gulcin, Taskapilioglu, Mevlut Ozgur, Tunca, Berrin, Bekar, Ahmet, Demirci, Hilal, Kocaeli, Hasan, Aksoy, Secil Ak, Egeli, Unal, Cecener, Gulsah, Tolunay, Sahsine
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - pharmacology; Bevacizumab - pharmacology; Cell Line, Tumor; Cell Movement - drug effects; Drug Synergism; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma cancer stem cell; Humans; Internal Medicine; Invasion; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical Education; MMP2; MMP9; Neoplasm Invasiveness - pathology; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Olea - chemistry; Olea europaea leaf extract; Plant Extracts - pharmacology; Plant Leaves - chemistry; Vascular Endothelial Growth Factor A - metabolism; VEGFA
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.04.022

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 (2 mg/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.