Direct oxidative DNA damage, apoptosis and radio sensitivity by spermine oxidase activities in mouse neuroblastoma cells

R. Amendola, A. Bellini, M. Cervelli, P. Degan, L. Marcocci, F. Martini, P. Mariottini

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

In mammals, the polyamines affect cell growth, differentiation, and apoptosis; their levels are increased in malignant and proliferating cells, thus justifying an interest in a chemotherapeutic approach to cancer. The flavoprotein SMO is the most recently characterized catabolic enzyme, preferentially oxidizing SPM to SPD, 3-aminopropanal and H 2O 2. In this report, we describe a novel functional characterization of the recently cloned splice variant isoforms from mouse brain, encoding, among others, the nuclear co-localized spermine oxidase mSMOμ. The over-expression of the active isoforms mSMOα and mSMOμ, and the inactive mSMOδ and mSMOγ in mouse neuroblastoma cells, demonstrated the first evidence of the direct oxidative DNA damage by the SMO activities, either alone or, in a higher extent, when associated with radiation exposure, thus working as radio sensitizer. These effects were reverted by treatment with 50 μM and 100 μM doses of the inhibitor of SMO activity MDL 72,527. The over-expression of all SMO isoforms failed to influence the expression of the regulating enzymes of polyamines metabolism ODC and SSAT. Dealing with the unbalanced tissue specific SMO activities, these results could indicate a new direction to tailor chemotherapy-associated radiotherapy, improving dose-rate protocol and allowing the modulation of deleterious side effects on healthy tissues.

Original languageEnglish
Pages (from-to)15-24
Number of pages10
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Volume1755
Issue number1
DOIs
Publication statusPublished - May 25 2005

Fingerprint

Radio
Neuroblastoma
DNA Damage
Protein Isoforms
Polyamines
Apoptosis
Flavoproteins
Enzymes
Cell Differentiation
Mammals
Radiotherapy
Drug Therapy
Brain
Growth
polyamine oxidase
Neoplasms
Therapeutics

Keywords

  • Apoptosis
  • DNA damage
  • Neuroblastoma
  • Oxidative stress
  • Polyamine
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Biophysics

Cite this

Direct oxidative DNA damage, apoptosis and radio sensitivity by spermine oxidase activities in mouse neuroblastoma cells. / Amendola, R.; Bellini, A.; Cervelli, M.; Degan, P.; Marcocci, L.; Martini, F.; Mariottini, P.

In: Biochimica et Biophysica Acta - Reviews on Cancer, Vol. 1755, No. 1, 25.05.2005, p. 15-24.

Research output: Contribution to journalArticle

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