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.
Highlights
Neuroblastoma (NB), a neural crest-derived pediatric cancer, is the most common extra-cranial solid tumor of infancy, accounting for about 7% of all malignancy diagnosed under the age of 15 years [1,2]
The cell viability of IMR-32 and HTLA230 cells was reduced by the lowest dose of olive leaf extract (OLE), while only the highest concentrations of OLE significantly affected the cell viability of SH-SY5Y and SK-N-AS
This study demonstrates for the first time the anti-tumor effects of olive leaf extract (OLE) against NB cells by investigating cell viability, cell proliferation, cell cycle progression, apoptosis, and migration in vitro
Summary
Neuroblastoma (NB), a neural crest-derived pediatric cancer, is the most common extra-cranial solid tumor of infancy, accounting for about 7% of all malignancy diagnosed under the age of 15 years [1,2] It is the most common cancer diagnosed during the first year of life, with a median age at diagnosis of 17 months [2]. Based on disease staging and risk factors assessment, the international NB risk group (INRG) stratifies patients into very low, low, intermediate, and high risk. This classification addresses the type of treatment to be undertaken [3]. The application of an intensive treatment schedule, which involves a phase of induction chemotherapy followed by surgery, myeloablative therapy combined with hematopoietic stem cells transplantation and local radiotherapy, and maintenance with anti-disialoganglioside (GD2) antibody plus isotrenoin, the survival rate for high-risk
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