EFFECT OF SPERMINE AND SPERMINE OXIDASE INHIBITORS ON THE EXPRESSION OF ORNITHINE DECARBOXYLASE AND PROTEINS REGULATING PROTEINS IN PROSTATE CANCER CELLS
DOI:
https://doi.org/10.15407/oncology.2025.02.119Keywords:
spermine, spermine oxidase inhibitors, ODC1, AZIN1, c-Myc, Bcl-XL, LNCaP and DU- 145 cell linesAbstract
Summary. Aim: to study the effect of spermine (Spn), spermine oxidase inhibitors (SMO), and their combined action on the expression of proteins involved in growth processes (ODC1, AZIN1, c-Myc and Bcl-XL) in human prostate cancer (PCa) cell lines. Object and methods: the study was performed on human prostate cancer cell cultures — androgen-sensitive (LNCaP) and androgenresistant (DU-145) lines. Protein expression was determined by Western blotting. Results: cultivation of tumor cells with Spn or Spn in combination with SMO inhibitors (chlorhexidine (CH) and MDL 72527) led to inhibition of tumor cell viability and was accompanied by a decrease in the expression of ornithine decarboxylase (ODC1) in the cells. The introduction of SMO inhibitors alone had little effect on ODC1 expression in both LNCaP and DU- 145 cells. The expression level of the antizyme inhibitor (AZIN1), as well as the level of ODC1, decreased under the action of SMO and under the combined action of SMO and CHO in cells of both lines. Changes in c-Myc expression in the cells were synchronous with changes in ODC1 expression. It was also found that incubation of tumor cells with Spn or with Spn combined with SMO inhibitors (MDL 72527 and CH) significantly reduced the expression of Bcl-XL in both cell lines. Conclusions: the results confirm the important role of spermine in the development of prostate cancer and complement the data on the possible mechanisms of growth-inhibitory action of Spn and SMO inhibitors, including their effect on the expression of proteins of ODC1 and AZIN1 genes involved in polyamine metabolism and proteins of c-Myc and Bcl-XL genes involved in growth and apoptosis. The data obtained indicate the importance of further studying the effect of Spn and its combinations with SMO inhibitors on the development of PCa as promising therapeutic agents.
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