Differentiation-Dependent Effects of a New Recombinant Manganese Superoxide Dismutase on Human SK-N-BE Neuron-Like Cells

  • Alessio Crestini
  • Rosa Vona
  • Maria Lo Giudice
  • Marco Sbriccoli
  • Paola Piscopo
  • Antonella Borrelli
  • Roberto Rivabene
  • Laura Ricceri
  • Aldo Mancini
  • Annamaria ConfaloniEmail author
Original Paper


We have recently isolated a new isoform of recombinant manganese superoxide dismutase (rMnSOD) which provides a potent antitumor activity and strongly counteracts the occurrence of oxidative stress and tissue inflammation. This isoform, in addition to the enzymatic action common to all SODs, also shows special functional and structural properties, essentially due to the presence of a first leader peptide that allows the protein to enter easily into cells. Among endogenous antioxidants, SOD constitutes the first line of natural defence against pathological effects induced by an excess of free radicals. Here, we firstly describe the effects of our rMnSOD administration on the proliferant and malignant undifferentiated human neuroblastoma SK-N-BE cell line. Moreover, we also test the effects of rMnSOD in the all trans retinoic-differentiated SK-N-BE neuron-like cells, a quiescent “not malignant” model. While rMnSOD showed an antitumor activity on proliferating cells, a poor sensitivity to rMnSOD overload in retinoid-differentiated neuron-like cells was observed. However, in the latter case, in presence of experimental-induced oxidative stress, overcharge of rMnSOD enhanced the oxidant effects, through an increase of H2O2 due to low activity of both catalase and glutathione peroxidase. In conclusion, our data show that rMnSOD treatment exerts differential effects, which depend upon both cell differentiation and redox balance, addressing attention to the potential use of the recombinant enzyme on differentiated neurons. These facts ultimately pave the way for further preclinical studies aimed at evaluation of rMnSOD effects in models of neurodegenerative diseases.


Recombinant human manganese superoxide dismutase Oxidative stress Free radicals SK-N-BE Neurodegeneration 



All-trans retinoic acid

Beta-amyloid peptide








Glutamic acid


Glutathione peroxidase


Menadione quinone


3-[3,4-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide


Reactive oxygen species


Recombinant manganese superoxide dismutase



This work was partially supported by Lega Italiana (Na) per la Lotta Contro i Tumori (LILT). Authors thank Mirko Morrone for its technical help to the experimental activity.

Author Contributions

AC designed and performed experiments, analyzed data and wrote the manuscript; MLG, MS and RR performed experiments; RV, LR and PP contributed to the interpretation of results and made manuscript revisions; AB and AM provided essential materials; AmC conceived the study and wrote the manuscript. All authors read and approved the manuscript.

Compliance with Ethical Standards

Conflict of interest

AM is the founder of Laedhexa Biotechnologies Inc. The others authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Alessio Crestini
    • 1
  • Rosa Vona
    • 2
  • Maria Lo Giudice
    • 1
  • Marco Sbriccoli
    • 1
  • Paola Piscopo
    • 1
  • Antonella Borrelli
    • 3
  • Roberto Rivabene
    • 1
  • Laura Ricceri
    • 4
  • Aldo Mancini
    • 5
  • Annamaria Confaloni
    • 1
    Email author return OK on get
  1. 1.Department of NeuroscienceItalian National Institute of HealthRomeItaly
  2. 2.Biomarkers Unit, Center for Gender-Specific MedicineItalian National Institute of HealthRomeItaly
  3. 3.Molecular Biology and Viral Oncology Unit, Department of Experimental OncologyIstituto Nazionale Tumori, “Fondazione G. Pascale”, IRCCSNaplesItaly
  4. 4.Centre for Behavioural Sciences and Mental HealthItalian National Institute of HealthRomeItaly
  5. 5.Leadhexa Biotechnologies Inc.San FranciscoUSA

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