Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells

article

Liberal, Joana
Carmo, Anália
Gomes, Célia
Cruz, Maria Teresa
Batista, Maria Teresa

Springer US

Liberal, J., Carmo, A., Gomes, C. et al. Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells. Invest New Drugs (2017). https://doi.org/10.1007/s10637-017-0483-7

0167-6997

10.1007/s10637-017-0483-7

Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells

Apoptosis
Cell cycle
Ellagitannins
Intracellular signaling pathways
UMUC3
Urolithins

CENTRO-01-0145-FEDER-000012-HealthyAging2020
COMPETE 2020 Operational Programme for Competitiveness and Internationalisation
POCI-01-0145-FEDER-007440
Ph.D. fellowship SFRH/BD/72918/2010

2017-11-07T15:50:17Z
2017-11-07T15:50:17Z
2017-07-20

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.
info:eu-repo/semantics/publishedVersion

openAccess
http://creativecommons.org/licenses/by/4.0/

eng