The MAO-B Inhibitor Selegiline Reduces the Viability of Different Prostate Cancer Cell Lines and Enhances the Effects of Anti-Androgen and Cytostatic Agents.

The current treatments for advanced prostate adenocarcinoma (PAC) include the androgen receptor antagonist enzalutamide and docetaxel-based chemotherapy. Elevated monoamine oxidase-A (MAO-A) mRNA expression and activity in tumorous prostate positively correlate with disease progression and therapy resistance. While MAO-B mRNA expression was also demonstrated in PAC cell lines, its role remained unclear. Therefore, this study evaluates the effects of the irreversible MAO-B inhibitor selegiline and rasagiline and their combinations with conventional therapies on androgen-insensitive (PC-3, DU145) and androgen-sensitive (22Rv1, LNCaP, VCaP) PAC cell lines. MAO activity was determined by the MAO-Glo luminescence assay, viability by the ATP-based chemiluminescence method, proliferation by the Luna-II automated cell counter, and mRNA expressions by RT-qPCR. MAO-B mRNA was stably expressed by all PAC cell lines, with the highest expression in 22Rv1 and LNCaP cells. Selegiline reduced MAO-B activity by 75%-80% and decreased cell counts by 40%-50% at 100 μM in PC-3 and 22Rv1 cells. Selegiline concentration-dependently inhibited cell proliferation (100 μM-10 mM) and reduced viability (1-10 mM) similar to rasagiline in all cell lines. Combination with enzalutamide in 22Rv1, and with docetaxel in PC-3 demonstrated potentiating and additive effects, respectively. Selegiline reduced FOXA1 and GLUT1 mRNA expressions related to cancer progression and metabolism in both cell lines, increased the apoptosis-related BAX in PC-3, and decreased AR, EGFR, and SNAI2 in 22Rv1 linked to proliferation and metastasis. These findings suggest potential for selegiline repurposing in both androgen-sensitive and -insensitive PAC therapy by promoting apoptosis and inhibiting cancer growth and survival signals, respectively.