Artículo
Comparative cytotoxic activity of hydroxytyrosol and its semisynthetic lipophilic derivatives in prostate cancer cells
Autor/es | León González, Antonio José
Sáez Martínez, Prudencio Jiménez Vacas, Juan M. Herrero Aguayo, Vicente Montero Hidalgo, Antonio J. Gómez Gómez, Enrique Madrona, Andrés Castaño, Justo P. Espartero Sánchez, José Luis Gahete, Manuel D. Luque, Raúl M. |
Departamento | Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica Universidad de Sevilla. Departamento de Farmacología |
Fecha de publicación | 2021 |
Fecha de depósito | 2021-09-10 |
Publicado en |
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Premios | Premio Mensual Publicación Científica Destacada de la US. Facultad de Farmacia |
Resumen | A high adherence to a Mediterranean diet has been related to numerous beneficial effects in human health, including a lower incidence and mortality of prostate cancer (PCa). Olive oil is an important source of phenolic ... A high adherence to a Mediterranean diet has been related to numerous beneficial effects in human health, including a lower incidence and mortality of prostate cancer (PCa). Olive oil is an important source of phenolic bioactive compounds, mainly hydroxytyrosol (HT), of this diet. Be-cause of the growing interest of this compound and its derivatives as a cancer chemopreventive agent, we aimed to compare the in vitro effect of HT isolated from olive mill wastewaters and five semisynthetic alkyl ether, ester, and nitro-derivatives against prostate cancer (PCa) cell lines. The effect in cell proliferation was determined in RWPE-1, LNCaP, 22Rv1, and PC-3 cells by resazurin assay, the effect in cell migration by wound healing assay, and tumorsphere and colony formation were evaluated. The changes in key signaling pathways involved in carcinogenesis were assessed by using a phosphorylation pathway profiling array and by Western blotting. Antiproliferative effects of HT and two lipophilic derivatives [hydroxytyrosyl acetate (HT-Ac)/ethyl hydroxytyrosyl ether (HT-Et)] were significantly higher in cancerous PC-3 and 22Rv1 cells than in non-malignant RWPE-1 cells. HT/HT-Ac/HT-Et significantly reduced migration capacity in RWPE-1 and PC-3 and prostatosphere size and colony formation in 22Rv1, whereas only HT-Ac and HT-Et reduced these functional parameters in PC-3. The cytotoxic effect in 22Rv1 cells was correlated with modifications in the phosphorylation pattern of key proteins, including ERK1/2 and AKT. Consistently, HT-Ac and HT-Et decreased p-AKT levels in PC-3. In sum, our results suggest that HT and its lipophilic derivatives could be considered as potential therapeutic tools in PCa. |
Identificador del proyecto | PI-0152-2019
BIO-0139 RH-0084-2020 PID2019-105564RB-I00 PID2019-105201RB-100 FPU17/00263 FPU16/06190 FPU18/02485 |
Cita | León González, A.J., Sáez Martínez, P., Jiménez Vacas, J.M., Herrero Aguayo, V., Montero Hidalgo, A.J., Gómez Gómez, E.,...,Luque, R.M. (2021). Comparative cytotoxic activity of hydroxytyrosol and its semisynthetic lipophilic derivatives in prostate cancer cells. Antioxidants, 10 (9), 1348. |
Ficheros | Tamaño | Formato | Ver | Descripción |
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Comparative Cytotoxic Activity.pdf | 3.450Mb | [PDF] | Ver/ | |