Redox Report (Jan 2021)

Redox imbalance induced by docetaxel in the neuroblastoma SH-SY5Y cells: a study of docetaxel-induced neuronal damage

  • Lucia Micheli,
  • Giulia Collodel,
  • Elena Moretti,
  • Daria Noto,
  • Andrea Menchiari,
  • Daniela Cerretani,
  • Sergio Crispino,
  • Cinzia Signorini

DOI
https://doi.org/10.1080/13510002.2021.1884802
Journal volume & issue
Vol. 26, no. 1
pp. 18 – 28

Abstract

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Objectives In cancer survivors, chemotherapy-associated adverse neurological effects are described as side effects in non-targeted tissue. We investigated the role of redox-imbalance in neuronal damage by a relative low dose of Docetaxel (DTX). Methods The neuroblastoma cells (SH-SY5Y cells) were exposed to DTX at a dose of 1.25 nM for 6 h. Antioxidant defenses (i.e. ascorbic acid, glutathione, and catalase) and lipid oxidation products (i.e. F2-isoprostanes) were evaluated. To investigate cell ultrastructure and tubulin localisation, transmission electron microscopy (TEM) and immunofluorescence techniques were applied. Results In the SH-SY5Y cells, DTX induced a significant reduction of total glutathione (P < 0.001) and ascorbic acid (P < 0.05), and an increase in both total F2-Isoprostanes (P < 0.05) and catalase activity (P < 0.05), as compared to untreated cells. Additionally, TEM showed a significant increase in cells with apoptotic characteristics. Immunolocalisation of tubulin showed a compromised cytoskeletal organisation. Discussion The investigated sublethal dose of DTX, to which non-targeted cells may be exposed throughout the duration of chemotherapy treatment, induces a redox imbalance resulting in a specific modulation of the antioxidant response. This study provides new insights into DTX-induced cellular mechanisms useful for evaluating whether the concomitant use of antioxidants associated with chemotherapy mitigates chemotherapy side effects in cancer survivors.

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