Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments

Amendola,Roberto; Cervelli,Manuela; Fratini,Emiliano; Sallustio,Davide   E.; Tempera,Giampiero; Ueshima,Taichi; Mariottini,Paolo; Agostinelli,Enzo

doi:10.3892/ijo.2013.2013

Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments

Authors:
- Roberto Amendola
- Manuela Cervelli
- Emiliano Fratini
- Davide E. Sallustio
- Giampiero Tempera
- Taichi Ueshima
- Paolo Mariottini
- Enzo Agostinelli
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Affiliations: ENEA, CR Casaccia, UT Bio-Rad RAB, I-00123 Rome, Italy, Department of Biology, University of ‘Roma Tre’, I-00146 Rome, Italy, Institute Pasteur Cenci-Bolognetti Foundation and Department of Biochemical Sciences ‘A. Rossi Fanelli’, University of Rome ‘Sapienza’ and CNR, Biology and Molecular Pathology Institutes, I-00185 Rome, Italy
Published online on: July 12, 2013 https://doi.org/10.3892/ijo.2013.2013
Pages: 813-820

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Abstract

The most frequent interventions in cancer therapy are currently the destruction of cells by irradiation or administration of drugs both able to induce radical formation and toxic metabolites by enzyme-catalyzed reactions. The aim of this study was to determine the cell viability of cells undergoing a DNA damage threshold accomplished by ROS overproduction via both ectopic expression of murine spermine oxidase (mSMOX) and bovine serum amine oxidase (BSAO) enzymes. Low dose of X-irradiation delivers a challenging dose of damage as evaluated in proficient Chinese hamster AA8 cell line and both deficient transcription-coupled nucleotide excision repair (NER) UV61 cells and deficient base excision repair (BER) EM9 cells, at 6 and 24 h after exposure. The priming dose of ROS overexposure by mSMOX provokes an adaptive response in N18TG2, AA8 and EM9 cell lines at 24 h. Interestingly, in the UV61 cells, ROS overexposure by mSMOX delivers an earlier adaptive response to radiation. The enzymatic formation of toxic metabolites has mainly been investigated on wild-type (WT) and multidrug-resistant (MDR) cancer cell lines, using and spermine as substrate of the BSAO enzyme. MDR cells are more sensitive to the toxic polyamine metabolites than WT cells, thus indicating a new therapeutic strategy to overcome MDR tumors. Since SMOX in mammals is differentially activated in a tissue-specific manner and cancer cells can differ in terms of DNA repair and MDR capabilities, it could be of interest to simultaneously treat with very low dose of X-rays and/or to alter SMOX metabolism to generate a differential response in healthy and cancer tissues.

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