THE EFFECT OF ALDEHYDE DEHYDROGENASE INHIBITORS AND THEIR COMBINATION WITH SPERMINE ON THE PROFILE OF POLYAMINES IN HUMAN PROSTATE CANCER CELL LINES
DOI:
https://doi.org/10.15407/oncology.2025.01.044Keywords:
поліаміни, спермін, госсипол, дисульфірам, клітинні лінії раку передміху- рової залози людиниAbstract
Summary. Aim: to investigate the effect of aldehyde dehydrogenase inhibitors, spermine (Spn) and their complex effect on the polyamine profile in human prostate cancer (PCa) cell lines and to compare changes in the polyamine profile with tumor cell survival. Object and methods: the study was conducted on cell cultures of androgen-sensitive (LNCaP) and androgen-resistant (DU-145) cell lines. The profile of polyamines in tumor cells was determined by high-performance liquid chromatography (HPLC). Results: the addition of Spn to the culture medium caused a significant accumulation of this polyamine in the cells. The use of aldehyde dehydrogenase inhibitors (gossypol and disulfiram) was accompanied by a decrease in the level of spermidine (Spd). Incubation of cells with Spn led to a decrease in the proliferation rate — the molar ratio Spd/Spn. Especially low values of the Spd/Spn ratio were observed when Spn was used in combination with aldehyde dehydrogenase inhibitors. When Spn was used in combination with aldehyde dehydrogenase inhibitors, cell survival rates were also the lowest. This indicated a more effective inhibition of cell growth with the combined use of these factors compared to their use separately, even in much higher concentrations. Conclusions: the use of aldehyde dehydrogenase inhibitors alone and in combination with Spn causes changes in the profile of polyamines in tumor cells characteristic of growth inhibition and a decrease in the molar ratio of Spd/Spn. These changes are more pronounced when these factors are used together and are accompanied by a decrease in the survival of androgen-sensitive (LNCaP) and androgen-resistant (DU-145) human prostate cancer cell lines. At the same time, the use of aldehyde dehydrogenase inhibitors together with Spn more effectively reduced the survival of androgen-sensitive LNCaP cells of human prostate compared to androgen-resistant DU-145 cells. The results obtained indicate the prospects for further study of SPN and its combinations with aldehyde hydrogenase inhibitors as potential treatment agents for PCa.
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