Abstract

Compounds of natural origin may constitute an interesting tool for the treatment of neuroblastoma, the most prevalent extracranial solid tumor in children. PRES is a commercially available food supplement, composed of a 13:2 (w/w) extracts mix of Olea europaea L. leaves (OE) and Hibiscus sabdariffa L. flowers (HS). Its potential towards neuroblastoma is still unexplored and was thus investigated in human neuroblastoma SH-SY5Y cells. PRES decreased the viability of cells in a concentration-dependent fashion (24 h IC50 247.2 ± 31.8 µg/mL). Cytotoxicity was accompanied by an increase in early and late apoptotic cells (AV-PI assay) and sub G0/G1 cells (cell cycle analysis), ROS formation, reduction in mitochondrial membrane potential, and caspases activities. The ROS scavenger N-acetyl-L-cysteine reverted the cytotoxic effects of PRES, suggesting a key role played by ROS in PRES-mediated SH-SY5Y cell death. Finally, the effects of OE and HS extracts were singularly tested and compared to those of the corresponding mixture. OE- or HS-mediated cytotoxicity was always significantly lower than that caused by PRES, suggesting a synergic effect. In conclusion, the present findings highlight the potential of PRES for the treatment of neuroblastoma and offers the basis for a further characterization of the mechanisms underlying its effects.

Highlights

  • Advanced therapeutic strategies for cancer are mainly based on synthetic drugs and/or monoclonal humanized antibodies, that often produce severe adverse effects, despite designed for being selective

  • PRES is a 13:2 (w/w) mix of the extracts prepared from Olea europaea L. leaves (OE) and Hibiscus sabdariffa L. flowers (HS), respectively

  • We found it of interest to assess whether the observed overall effect of PRES is a result of an additive, antagonistic or synergic activity between OE and HS components

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Summary

Introduction

Advanced therapeutic strategies for cancer are mainly based on synthetic drugs and/or monoclonal humanized antibodies, that often produce severe adverse effects, despite designed for being selective. The finding of non-toxic compounds, that still target particular genes or proteins should be a strategy that worth to be pursued, especially for pediatric cancer treatments. The diagnosis occurs mainly within the first year of age, resulting into a better outcome, whereas in the other patients the outcome itself is generally poor. NB treatment, despite some successes, remains highly demanding and is based on surgical resection, chemo- or radiation therapy. Surgery is not possible in more than 70% of patients as Antioxidants 2021, 10, 1962.

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