EFFECT OF SPERMININE AND ITS COMBINATION WITH SPERMINOXIDASE INHIBITORS ON THE PROFILE OF POLYAMINE AND SURVIVAL OF HUMAN PROSTATE CANCER CELLS

Abstract

Summary. Aim: to investigate the effect of spermine (Spn) and spermine oxidase inhibitors (SMO) and their effect in combination on the polyamine profile in human PCa cell lines and to compare the nature of polyamine changes with tumor cell viability. Object and methods: the study was performed on cell cultures of hormone-sensitive (LNCaP) and hormone-resistant (DU-145) cell lines. The profile of polyamines in tumor cells and the activities of spermine oxidase and polyamine oxidase (PAO) were determined by high-performance liquid chromatography. Results: the addition of Spn to the culture medium causes a significant accumulation of this polyamine in cells, a decrease in putrescine (Put) and spermidine (Spd). The use of SMO inhibitors (chlorhexidine and MDL-72527) is accompanied by a decrease in Spd levels and accumulation of acetylated spermidine (AcSpd). The use of Spn leads to a decrease in the proliferation rate — the molar ratio of spermidine/spermine (Spd/Spn). Particularly low values of the Spd/Spn ratio were observed when spermine was used in combination with SMO inhibitors. When Spn was used in combination with SMO inhibitors, the lowest cell viability rates were also observed, indicating a more effective inhibition of cell growth with the combined use of these factors compared to their use separately, even in significantly higher concentrations. The use of chlorhexidine and chlorhexidine together with spermine led to a decrease in the activity of SMO and PAO. Conclusions: the use of spermine and spermine in combination with SMO inhibitors leads to changes in the polyamine profile in tumor cells characteristic of growth inhibition (decrease in Spd, Put and increase in Spn) and a decrease in the molar ratio Spd/Spn. These changes are accompanied by a decrease in the survival of cells of hormone-sensitive (LNCaP) and hormone-resistant (DU-145) human prostate cancer lines. The obtained results show the prospects for further study of spermine and its combination with SMO inhibitors as potential agents for the treatment of prostate cancer.