Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

Manuela Cervelli, Gabriella Bellavia, Emiliano Fratini, Roberto Amendola, Fabio Polticelli, Marco Barba, Rodolfo Federico, Fabrizio Signore, Giacomo Gucciardo, Rosalba Grillo, Patrick M. Woster, Robert A Casero, Paolo Mariottini

Research output: Contribution to journalArticle

Abstract

Background: Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme.Methods: BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined.Results: Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors.Conclusions: This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials.

Original languageEnglish (US)
Article number555
JournalBMC Cancer
Volume10
DOIs
Publication statusPublished - Oct 14 2010

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

Cervelli, M., Bellavia, G., Fratini, E., Amendola, R., Polticelli, F., Barba, M., ... Mariottini, P. (2010). Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm. BMC Cancer, 10, [555]. https://doi.org/10.1186/1471-2407-10-555