Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm.
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.
Cervelli
Manuela
M
Dipartimento di Biologia, Università Roma Tre, Rome, Italy.
Bellavia
Gabriella
G
Fratini
Emiliano
E
Amendola
Roberto
R
Polticelli
Fabio
F
Barba
Marco
M
Federico
Rodolfo
R
Signore
Fabrizio
F
Gucciardo
Giacomo
G
Grillo
Rosalba
R
Woster
Patrick M
PM
Casero
Robert A
RA
Mariottini
Paolo
P
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000097667:Polyamine Oxidase
D000970:Antineoplastic Agents; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D011994:Recombinant Proteins; D013096:Spermine; D000097667:Polyamine Oxidase; C059685:N(1),N(11)-diethylnorspermine; C083629:N(1)-ethyl-N-(11)-((cyclopropyl)methyl)-4,8-diazaundecane-1,11-diamine