TY  - JOUR
AU  - Berning, Lena
AU  - Schlütermann, David
AU  - Friedrich, Annabelle
AU  - Berleth, Niklas
AU  - Sun, Yadong
AU  - Wu, Wenxian
AU  - Mendiburo, María José
AU  - Deitersen, Jana
AU  - Brass, Hannah
AU  - Skowron, Margaretha A.
AU  - Hoffmann, Michèle J.
AU  - Niegisch, Günter
AU  - Pietruszka, Jörg
AU  - Stork, Björn
TI  - Prodigiosin Sensitizes Sensitive and Resistant Urothelial Carcinoma Cells to Cisplatin Treatment
JO  - Molecules
VL  - 26
IS  - 5
SN  - 1420-3049
CY  - Basel
PB  - MDPI
M1  - FZJ-2021-03550
SP  - 1294 -
PY  - 2021
AB  - Cisplatin-based treatment is the standard of care therapy for urothelial carcinomas. However, complex cisplatin resistance mechanisms limit the success of this approach. Both apoptosis and autophagy have been shown to contribute to this resistance. Prodigiosin, a secondary metabolite from various bacteria, exerts different biological activities including the modulation of these two cellular stress response pathways. We analyzed the effect of prodigiosin on protein levels of different autophagy- and apoptosis-related proteins in cisplatin-sensitive and -resistant urothelial carcinoma cells (UCCs). Furthermore, we investigated the effect on cell viability of prodigiosin alone or in combination with cisplatin. We made use of four different pairs of cisplatin-sensitive and -resistant UCCs. We found that prodigiosin blocked autophagy in UCCs and re-sensitized cisplatin-resistant cells to apoptotic cell death. Furthermore, we found that prodigiosin is a potent anticancer agent with nanomolar IC50 values in all tested UCCs. In combination studies, we observed that prodigiosin sensitized both cisplatin-sensitive and -resistant urothelial carcinoma cell lines to cisplatin treatment with synergistic effects in most tested cell lines. These effects of prodigiosin are at least partially mediated by altering lysosomal function, since we detected reduced activities of cathepsin B and L. We propose that prodigiosin is a promising candidate for the therapy of cisplatin-resistant urothelial carcinomas, either as a single agent or in combinatory therapeutic approaches
LB  - PUB:(DE-HGF)16
C6  - 33673611
UR  - <Go to ISI:>//WOS:000628431800001
DO  - DOI:10.3390/molecules26051294
UR  - https://juser.fz-juelich.de/record/896717
ER  -