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

Authors

Manuela Cervelli, Dipartimento di Biologia, Università Roma TreFollow
Gabriella Bellavia, Dipartimento di Biologia, UniversitàFollow
Emiliano Fratini, Dipartimento di Biologia, UniversitàFollow
Roberto Amendola, Dipartimento BAS-BiotecMed, ENEAFollow
Fabio Polticelli, Dipartimento di Biologia, UniversitàFollow
Marco Barba, Dipartimento di Biologia, UniversitàFollow
Rodolfo Federico, Dipartimento di Biologia, UniversitàFollow
Fabrizio Signore, San Camillo-Forlanini HospitalFollow
Giacomo Gucciardo, San Camillo-Forlanini HospitalFollow
Rosalba Grillo, San Camillo-Forlanini HospitalFollow
Patrick M. Woster, Wayne State UniversityFollow
Robert A. Casero Jr, The Johns Hopkins University School of MedicineFollow
Paolo Mariottini, Dipartimento di Biologia, UniversitàFollow

Document Type

Article

Abstract

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.

Disciplines

Biochemistry | Oncology | Women's Health

Recommended Citation

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