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Ellagitannins have been gaining attention as potential anticancer molecules. However, the low bioavailability of ellagitannins and their extensive metabolization in the gastrointestinal tract into ellagic acid and urolithins suggest that the health benefits of consuming ellagitannins rely on the direct effects of their metabolites. Recently, chemopreventive and chemotherapeutic activities were ascribed to urolithins. Nonetheless, there is still a need to screen and evaluate the selectivity of these molecules and to elucidate their cellular mechanisms of action. Therefore, this work focused on the antiproliferative effects of urolithins A, B and C and ellagic acid on different human tumor cell lines. The evaluation of cell viability and the determination of the half-maximal inhibitory concentrations indicated that the sensitivity to the studied urolithins varied markedly between the different cell lines, with the bladder cancer cells (UMUC3) being the most susceptible. In UMUC3 cells, urolithin A was the most active molecule, promoting cell cycle arrest at the G2/M checkpoint, increasing apoptotic cell death and inhibiting PI3K/Akt and MAPK signaling. Overall, the present study emphasizes the chemopreventive/chemotherapeutic potential of urolithins, highlighting the stronger effects of urolithin A and its potential to target transitional bladder cancer cells.

O Projecto OTALEX foi financiado pelo programa europeu INTERREG IIIA e teve como objectivos estudar e dar a conhecer a realidade de um território, composto pelas regiões do Alentejo em Portugal e da Extremadura em Espanha, separadas convencionalmente pela fronteira administrativa mas unidas pelas suas características físicas, ambientais, sociais e económicas. Tratam-se de espaços rurais de baixa densidade demográfica onde os recursos naturais, culturais e a qualidade do ambiente constituem os seus atractivos fundamentais. A IDE OTALEX é o resultado do esforço, do compromisso e da colaboração entre instituições da fronteira, com implicação aos três níveis administrativos: Nacional, Regional e Local. Apresentam-se os trabalhos de homogeneização e estandartização de dados territoriais do Alentejo e da Extremadura, através de clientes de visualização de mapas, consulta de topónimos e de catálogo, no âmbito da directiva INSPIRE.