Non-selective beta-blockers as potential coadjutants for prostate cancer treatment

• Autor(a) principal: Frazão, Carolina Castanheiro
• Data de Publicação: 2021
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/33519
• topic: Beta-blockers; Cell lines; Prostate cancer; Cell viability; Combined treatments

Prostate cancer is the third most diagnosed type of cancer worldwide and the fifth leading cause of death in men. Currently, available treatments are not always effective. For this reason, new forms of treatment need to be explored, which may include the use of medications, already clinically available, for the treatment of other diseases, such as β-blockers. The present study aimed to explore the effects of various β-blockers and pharmaceuticals typically used in the treatment of prostate cancer on prostate cancer cell lines (22Rv1, LNCaP and PC3) and on a normal prostate tissue cell line (PNT-2). For this purpose, selected lines were exposed, up to 72 h, to a range of concentrations (10-250 or 0.1-100 μM) of non-selective β-blockers (propranolol and carvedilol), β1 blockers (metoprolol and atenolol), a cytostatic drug used in chemotherapy (cisplatin) and a drug that blocks the androgen receptor, used in hormonal therapy (flutamide) with cell viability assessed after the exposure period, using 3-(4,5- dimethylthiazol-2 -yl)-2,5-diphenyltetrazolium bromide (MTT). The results obtained reveal that selected non-selective β-blockers as well as cytostatic drugs showed a cytotoxic effect in all cell lines, while the β1-blockers tested did not significantly alter cell viability, in the range of concentrations tested. Of the cell lines tested, 22Rv1 was the most sensitive to propranolol, carvedilol, and cisplatin, with the PC3 line showing the lowest sensitivity to the drugs tested. Based on the results of the individual exposures, the 22Rv1 (the most sensitive line), PC3 (the least sensitive line), and PNT-2 (the normal cell line) lines were subjected to a combined exposure of propranolol and cisplatin or propranolol and flutamide or cisplatin and flutamide in order to assess the potential β-blocker interaction with cytostatic compounds, in order to assess their potential application in combined treatments. Overall, the combined exposures revealed concentration-dependent interactions between cytostatic drugs and propranolol. Among the tested combinations, propranolol with cisplatin is the most promising for the treatment of this cancer.