Escola Superior de Saúde Dr. Lopes Dias, Instituto Politécnico de Castelo Branco, Campus da Talagueira, Avenida do Empresário, 6000-767, Castelo Branco, Portugal.
CNC.IBILI, University of Coimbra, 3004-504, Coimbra, Portugal.
Invest New Drugs. 2017 Dec;35(6):671-681. doi: 10.1007/s10637-017-0483-7. Epub 2017 Jun 20.
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.
鞣花单宁作为潜在的抗癌分子引起了人们的关注。然而，鞣花单宁的生物利用度低，在胃肠道中广泛代谢为鞣花酸和尿石素，这表明摄入鞣花单宁的健康益处依赖于其代谢物的直接作用。最近，尿石素被归因于化学预防和化学治疗活性。尽管如此，仍然需要筛选和评估这些分子的选择性，并阐明其细胞作用机制。因此，这项工作集中在尿石素 A、B 和 C 和鞣花酸对不同人类肿瘤细胞系的增殖抑制作用上。细胞活力评估和半最大抑制浓度的测定表明，研究的尿石素在不同细胞系之间的敏感性差异很大，膀胱癌细胞（UMUC3）最为敏感。在 UMUC3 细胞中，尿石素 A 是最活跃的分子，它能促进细胞周期在 G2/M 检查点停滞，增加凋亡细胞死亡，并抑制 PI3K/Akt 和 MAPK 信号通路。总的来说，本研究强调了尿石素的化学预防/化学治疗潜力，突出了尿石素 A 的更强作用及其靶向移行性膀胱癌细胞的潜力。
