THE EFFECT OF PARGILINE, SPERMINE AND THEIR COMBINATIONS ON ANDROGEN-DEPENDENT AND ANDROGEN-INDEPENDENT HUMAN PROSTATE CANCER CELLS in vitro
Authors:   R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Yanish Yu.V. , Zaletok S.P. ,   R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Voronina O.K. ,   Taras Shevchenko National University of Kyiv, Kyiv, Ukraine, Sumnikova I.O. ,   R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Stashenko V.O. ,   R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Klenov O.O. ,   R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Bentrad V.V. ,   R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
Published: November 2024

Summary. A series of studies on enhancing the cytotoxic effect of spermine on human prostate cells by affecting the enzymes of its metabolism has been continued. Aim: to investigate effects of pargyline, spermine and their combinations the survival, ζ-potential and surface charge and cytomorphological properties of human prostate cancer cells in culture. Object and methods: studies were conducted on cell cultures: differentiated androgen-dependent LNCaP cell line and low-differentiated androgen-independent DU-145 cell line. Cell survival was determined in the trypan blue assay. The effect of the investigated compounds, both individually and in combination, on the viability and proliferative activity of cells was assessed by the colorimetric method – by staining living cells with a solution of crystal violet in methanol. Biophysical parameters (ζ-potential and surface electric charge density) were determined according to the method cellular microelectrophoresis. Cytomorphological characteristics were studied on preparations of cells grown on coverslips, fixed and stained with hematoxylin and eosin (magnification 1000×). Results: for LNCaP cells, the IC50 of pargyline was 2.2 mM, and the IC50 of spermine was 1.5 mM. For DU-145 cells, the IC50 of pargyline was 2.35 mM, the IC50 of spermine was 5.0 mM. According to biophysical indicators, spermine caused an inversion of the sign of the electric charge in cells of the LNCaP line. Pargyline did not exert such an effect, the charge remained negative, demonstrating an inverse dependence on its concentration. The combination of pargyline and spermine increased the cytotoxic effect of spermine on LNCaP cells, but did not affect the value of their ζ-potential and surface charge density, the positive sign of which, caused by the effect of spermine, was preserved. At the same time, pargyline completely eliminated spermine-induced inversion of the sign of the total surface charge of DU-145 cells, returning it to the normal negative values. Conclusions: it is shown that the differentiated androgen-dependent cells of the LNCaP line with the combined use of pargyline and spermine demonstrated an enhancement of the cytotoxic effect of spermine. At the same time, low-differentiated cells of the DU-145 line, which do not have androgen receptors, were more resistant to the effects of both pargyline and pargyline in combination with spermine. Pargyline also reversed spermine-induced inversion of the sign of the total surface charge of DU-145 cells, returning it to normal negative values. Cytomorphological changes that occurred under the influence of both pargyline alone and in its combination with spermine demonstrate mainly the apoptotic pathway of cell death in the androgen-independent DU-145 line, while in the androgen-dependent LNCaP line, a smaller proportion of cells were in a state of apoptosis.