Publicação
Drug repurposing as an alternative in prostate cancer treatment
| Resumo: | Prostate cancer is the third most diagnosed cancer worldwide, and the second cause of cancer death in men. The currently available treatments are not always effective and may be associated with undesired side effects. There has been intense research to find more effective treatments. Among the different approaches being tested, drug repurposing emerges as an interesting alternative since it uses clinically studied and already approved drugs available in the market for a new clinical use. There are different potential drugs that may be potentially useful. In this sense, the goal of this study was to test the potential application of a β-blocker (carvedilol), a selective serotonin reuptake inhibitor (sertraline), a norepinephrine-dopamine reuptake inhibitor (bupropion) and an antimetabolite drug (5-fluorouracil), alone or in binary mixtures, on cancer treatment. Thus, the prostate cancer cell line (22Rv1) as well as the normal prostate cell line (PNT-2) were submitted to different concentrations of the drugs, carvedilol (0.1, 1, 5, 10, 20, 50, 75 and 100μM), sertraline (0.1, 0.5, 1, 5, 10, 20, 40 and 60μM), bupropion (1, 10, 50, 100, 200, 300, 400 and 500μM), 5-fluorouracil (0.1, 0.5, 1, 2, 5, 10, 30 and 50μM) and cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay after exposures of up to 72h. Overall, the tested conditions demonstrated the ability of the drugs to induce toxic effects and allowed the estimation of lethal concentrations (LCx). The cancer cell line demonstrated a higher sensitivity toward sertraline, bupropion and 5-fluorouracil and higher resistance to carvedilol when compared to the normal prostate cell line. Data from combined exposures conditions highlights the potential value of the use of 5-fluorouracil with sertraline supporting that drug repurposing of these pharmaceuticals may be a valuable approach in prostate cancer treatment, providing initial data that may be valuable for clinical tests. Combined exposures of carvedilol with sertraline hydrochloride indicate that the intake of both pharmaceuticals is not recommended, providing valuable data from a clinical standpoint. |
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| Autores principais: | Cunha, Leandro da Silva |
| Assunto: | Cell viability Combined treatments Drug repurposing Prostate cancer |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Aveiro |
| Idioma: | inglês |
| Origem: | RIA - Repositório Institucional da Universidade de Aveiro |
| Resumo: | Prostate cancer is the third most diagnosed cancer worldwide, and the second cause of cancer death in men. The currently available treatments are not always effective and may be associated with undesired side effects. There has been intense research to find more effective treatments. Among the different approaches being tested, drug repurposing emerges as an interesting alternative since it uses clinically studied and already approved drugs available in the market for a new clinical use. There are different potential drugs that may be potentially useful. In this sense, the goal of this study was to test the potential application of a β-blocker (carvedilol), a selective serotonin reuptake inhibitor (sertraline), a norepinephrine-dopamine reuptake inhibitor (bupropion) and an antimetabolite drug (5-fluorouracil), alone or in binary mixtures, on cancer treatment. Thus, the prostate cancer cell line (22Rv1) as well as the normal prostate cell line (PNT-2) were submitted to different concentrations of the drugs, carvedilol (0.1, 1, 5, 10, 20, 50, 75 and 100μM), sertraline (0.1, 0.5, 1, 5, 10, 20, 40 and 60μM), bupropion (1, 10, 50, 100, 200, 300, 400 and 500μM), 5-fluorouracil (0.1, 0.5, 1, 2, 5, 10, 30 and 50μM) and cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay after exposures of up to 72h. Overall, the tested conditions demonstrated the ability of the drugs to induce toxic effects and allowed the estimation of lethal concentrations (LCx). The cancer cell line demonstrated a higher sensitivity toward sertraline, bupropion and 5-fluorouracil and higher resistance to carvedilol when compared to the normal prostate cell line. Data from combined exposures conditions highlights the potential value of the use of 5-fluorouracil with sertraline supporting that drug repurposing of these pharmaceuticals may be a valuable approach in prostate cancer treatment, providing initial data that may be valuable for clinical tests. Combined exposures of carvedilol with sertraline hydrochloride indicate that the intake of both pharmaceuticals is not recommended, providing valuable data from a clinical standpoint. |
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