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Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

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

Authors: 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 Jr, Paolo Mariottini

Published in: BMC Cancer | Issue 1/2010

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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.
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Metadata
Title
Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm
Authors
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 Jr
Paolo Mariottini
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-555

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