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Reduction of oxidative stress and ornithine decarboxylase expression in a human prostate cancer cell line PC-3 by a combined treatment with α-tocopherol and naringenin

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Abstract

Differentiation of a human aggressive PC-3 cancer cell line was obtained, in a previous investigation, by the synergic effect of α-tocopherol (α-TOC) and naringenin (NG). This combined treatment induced apoptosis and subsequent reduction of the PC-3 cell proliferation and invasion, by a pro-differentiating action. Since one of the peculiar characteristics of NG and α-TOC is their strong antioxidant activity, this study aimed to investigate their potential effect on the activity of the main enzymes involved in the antioxidant mechanism in prostate cancer cells. NG and α-TOC administered singularly or combined in the PC-3 cell line, affected the activity of several enzymes biomarkers of the cellular antioxidant activity, as well as the concentration of total glutathione (GSH + GSSG) and thiobarbituric acid reactive substances (TBARS). The combined treatment increased the TBARS levels and superoxide dismutase (SOD) activity, while decreased the glutathione S-transferase (GST), glutathione reductase (GR), and glyoxalase I (GI) activities. The results obtained indicate that a combined treatment with these natural compounds mitigated the oxidative stress in the human PC-3 cell line. In addition, a significant reduction of both ornithine decarboxylase (ODC) expression and intracellular levels of polyamines, both well-known positive regulators of cell proliferation, accompanied the reduction of oxidative stress observed in the combined α-TOC and NG treatment. Considering the established role of polyamines in cell differentiation, the synergism with NG makes α-TOC a potential drug for further study on the differentiation therapy in prostate cancer patients.

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Abbreviations

ODC:

Ornithine decarboxylase

NG:

Naringenin

α-TOC:

α-Tocopherol

AR:

Androgen receptor

PSA:

Specific prostate antigen

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Acknowledgements

Tabolacci C. was a recipient of fellowship funded by Fondazione Umberto Veronesi that is gratefully acknowledged. The research was funded thanks to a generous contribution from the Scientific Association ARSS Italy.

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Authors and Affiliations

  1. Department of Urology, Cardarelli Hospital, Campobasso, Italy

    Piera Torricelli

  2. Department of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, Italy

    Antonia Concetta Elia & Gabriele Magara

  3. Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy

    Giordana Feriotto

  4. Department of Biology, University of Tor Vergata, Rome, Italy

    Cinzia Forni, Angelo De Martino & Simone Beninati

  5. Department of Physics, University of Tor Vergata, Rome, Italy

    Ilaria Borromeo

  6. Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy

    Claudio Tabolacci

  7. Department of Neuroscience and Rehabilitation, University of Ferrara, via Luigi Borsari 46, 44121, Ferrara, Italy

    Carlo Mischiati

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  1. Piera Torricelli
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  2. Antonia Concetta Elia
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Correspondence to Carlo Mischiati.

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Torricelli, P., Elia, A.C., Magara, G. et al. Reduction of oxidative stress and ornithine decarboxylase expression in a human prostate cancer cell line PC-3 by a combined treatment with α-tocopherol and naringenin. Amino Acids 53, 63–72 (2021). https://doi.org/10.1007/s00726-020-02925-1

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  • DOI: https://doi.org/10.1007/s00726-020-02925-1

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