Open Access Research article

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

Manuela Cervelli1, Gabriella Bellavia1, Emiliano Fratini12, Roberto Amendola2, Fabio Polticelli1, Marco Barba1, Rodolfo Federico1, Fabrizio Signore3, Giacomo Gucciardo3, Rosalba Grillo3, Patrick M Woster4, Robert A Casero5 and Paolo Mariottini1*

Author Affiliations

1 Dipartimento di Biologia, Università Roma Tre, Rome, Italy

2 Dipartimento BAS-BiotecMed, ENEA, CR Casaccia, Rome, Italy

3 Department of Gynaecology, Breast Surgery and Pathology, San Camillo-Forlanini Hospital, Rome, Italy

4 Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA

5 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA

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BMC Cancer 2010, 10:555  doi:10.1186/1471-2407-10-555

Published: 14 October 2010

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.