The Olive Leaves Extract Has Anti-Tumor Effects against Neuroblastoma through Inhibition of Cell Proliferation and Induction of Apoptosis

Abstract

Neuroblastoma (NB) is the most common extra-cranial solid tumor of pediatric age. The prognosis for high-risk NB patients remains poor, and new treatment strategies are desirable. The olive leaf extract (OLE) is constituted by phenolic compounds, whose health beneficial effects were reported. Here, the anti-tumor effects of OLE were investigated in vitro on a panel of NB cell lines in terms of (i) reduction of cell viability; (ii) inhibition of cell proliferation through cell cycle arrest; (iii) induction of apoptosis; and (iv) inhibition of cell migration. Furthermore, cytotoxicity experiments, by combining OLE with the chemotherapeutic topotecan, were also performed. OLE reduced the cell viability of NB cells in a time- and dose-dependent manner in 2D and 3D models. NB cells exposed to OLE underwent inhibition of cell proliferation, which was characterized by an arrest of the cell cycle progression in G0/G1 phase and by the accumulation of cells in the sub-G0 phase, which is peculiar of apoptotic death. This was confirmed by a dose-dependent increase of Annexin V+ cells (peculiar of apoptosis) and upregulation of caspases 3 and 7 protein levels. Moreover, OLE inhibited the migration of NB cells. Finally, the anti-tumor efficacy of the chemotherapeutic topotecan, in terms of cell viability reduction, was greatly enhanced by its combination with OLE. In conclusion, OLE has anti-tumor activity against NB by inhibiting cell proliferation and migration and by inducing apoptosis.

Anti-ulcer properties, cytokines, and apoptosis regulatory effects of Olea europaea leaves from Hail Province, Saudi Arabia

“…Caspase-9 is a protease that is involved in the apoptotic process, and has been related to mitochondrial damage. An earlier study suggested that aqueous OLE exhibited anti-apoptosis markers by reducing the levels of caspases 3 and 9 due to the presence of oleuropein and hydroxytyrosol (Morandi et al, 2021). Yaguchi et al (2010) reported the inhibitory effect of linoleic acid on caspases 3 and 9.…”

Isoquercitrin restrains the proliferation and promotes apoptosis of human osteosarcoma cells by inhibiting the Wnt/β-catenin pathway

“…Researchers have shown that the anti-tumor effects of many drugs can be achieved by inducing tumor cell apoptosis [ [16] , [17] , [18] ]. To prove this, 143B cells were treated with 20 and 40 μM concentrations of ISO.…”

Hibiscus Flower and Olive Leaf Extracts Activate Apoptosis in SH-SY5Y Cells

“…Moreover, the present results suggest that the interesting activity of PRES was due to all its components and not only to oleuropein-like compounds, the most representative from a quantitative point of view. Data from the literature assessing OE leaf extract anti-tumor activity against different neuroblastoma cell lines, including SH-SY5Y, reported significant loss in cell viability and apoptosis after 72 h treatment with the extract containing 300 µM oleuropein [ 33 ]. Seçme et al directly investigated the anti-tumor efficacy of the single bioactive molecule oleuropein against the SH-SY5Y neuroblastoma cell line, finding an approximate 48 hour-IC 50 of 350 µM [ 34 ].…”