Abstract
BackgroundPolyamine 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.MethodsBC 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.ResultsBoth 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.ConclusionsThis 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.
Highlights
Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC)
To determine the incidence of spermine (Spm) analogues in BC treatments, we previously evaluated the level of spermine oxidase (SMO) expression in BC tissues
SMO enzyme is an important PA catabolic component that could play a crucial role in BC disease and still remains a promising therapeutic target for cancer and hyperproliferation
Summary
Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was carried out to test their property in silico and in vitro on the recombinant SMO enzyme. An analysis of spermidine/spermine N1-acetyltransferase (SSAT) and N1-acetylpolyamine oxidase (APAO) enzyme activities in human BC tissue has been carried out by Wallace et al [12]. This analysis correlates the higher level of acetylated polyamines (acetylPA) in malignant tumors, with the decreasing activity of APAO, concurrent with the increase of SSAT activity [12]
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