Effect of rMnSOD on survival signaling in pediatric high risk T-cell acute lymphoblastic leukaemia

A. Pica, A. Di Santi, V. D'angelo, A. Iannotta, M. Ramaglia, M. Di Martino, M. L. Pollio, A. Schiattarella, A. Borrelli, A. Mancini, P. Indolfi, F. Casale

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Abstract

Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that defends against oxidative damage due to reactive oxygen species (ROS). A new isoform of MnSOD with cytotoxic activity was recently discovered in liposarcoma cells. Here, we tested the effectiveness of a recombinant form of this isoform (rMnSOD) on leukemic T cells, Jurkat cells, and lymphocytes. Our results confirm that leukemic T cells can internalize rMnSOD and that rMnSOD causes apoptosis of 99% of leukemic cells without showing toxic effects on healthy cells. Using light and electron microscopy, we determined that an rMnSOD concentration of 0.067μM most effective on apoptosis induction. Western blot analysis showed that treatment with 0.067μM rMnSOD resulted in high expression of the pro-apoptotic protein Bax and low expression of the anti-apoptotic protein Bcl-2 in leukemia cells. Concerning signal transduction pathway no influence was observed after treatment except for Jurkat cells showing a slightly decreased expression of ERK phosphorylation. These results suggest that rMnSOD may be an effective and non-toxic treatment option for T-cell leukemia. J. Cell. Physiol. 230: 1086-1093, 2015.

Original languageEnglish
Pages (from-to)1086-1093
Number of pages8
JournalJournal of Cellular Physiology
Volume230
Issue number5
DOIs
Publication statusPublished - May 1 2015

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
T-cells
Apoptosis Regulatory Proteins
Superoxide Dismutase
Protein Isoforms
Jurkat Cells
Apoptosis
Signal transduction
Phosphorylation
Lymphocytes
Poisons
Electron microscopy
Optical microscopy
Reactive Oxygen Species
T-Lymphocytes
T-Cell Leukemia
Liposarcoma
Cells
Enzymes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Medicine(all)

Cite this

Pica, A., Di Santi, A., D'angelo, V., Iannotta, A., Ramaglia, M., Di Martino, M., ... Casale, F. (2015). Effect of rMnSOD on survival signaling in pediatric high risk T-cell acute lymphoblastic leukaemia. Journal of Cellular Physiology, 230(5), 1086-1093. https://doi.org/10.1002/jcp.24840

Effect of rMnSOD on survival signaling in pediatric high risk T-cell acute lymphoblastic leukaemia. / Pica, A.; Di Santi, A.; D'angelo, V.; Iannotta, A.; Ramaglia, M.; Di Martino, M.; Pollio, M. L.; Schiattarella, A.; Borrelli, A.; Mancini, A.; Indolfi, P.; Casale, F.

In: Journal of Cellular Physiology, Vol. 230, No. 5, 01.05.2015, p. 1086-1093.

Research output: Contribution to journalArticle

Pica, A, Di Santi, A, D'angelo, V, Iannotta, A, Ramaglia, M, Di Martino, M, Pollio, ML, Schiattarella, A, Borrelli, A, Mancini, A, Indolfi, P & Casale, F 2015, 'Effect of rMnSOD on survival signaling in pediatric high risk T-cell acute lymphoblastic leukaemia', Journal of Cellular Physiology, vol. 230, no. 5, pp. 1086-1093. https://doi.org/10.1002/jcp.24840
Pica A, Di Santi A, D'angelo V, Iannotta A, Ramaglia M, Di Martino M et al. Effect of rMnSOD on survival signaling in pediatric high risk T-cell acute lymphoblastic leukaemia. Journal of Cellular Physiology. 2015 May 1;230(5):1086-1093. https://doi.org/10.1002/jcp.24840
Pica, A. ; Di Santi, A. ; D'angelo, V. ; Iannotta, A. ; Ramaglia, M. ; Di Martino, M. ; Pollio, M. L. ; Schiattarella, A. ; Borrelli, A. ; Mancini, A. ; Indolfi, P. ; Casale, F. / Effect of rMnSOD on survival signaling in pediatric high risk T-cell acute lymphoblastic leukaemia. In: Journal of Cellular Physiology. 2015 ; Vol. 230, No. 5. pp. 1086-1093.
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