TY  - JOUR
A1  - Rutz, Jochen
A1  - Maxeiner, Sebastian
A1  - Jüngel, Eva
A1  - Chun, Felix
A1  - Tsaur, Igor
A1  - Blaheta, Roman A.
T1  - Olive mill wastewater inhibits growth and proliferation of cisplatin- and gemcitabine-resistant bladder cancer cells in vitro by down-regulating the Akt/mTOR-signaling pathway
T2  - Nutrients
N2  - Bladder cancer patients whose tumors develop resistance to cisplatin-based chemotherapy often turn to natural, plant-derived products. Beneficial effects have been particularly ascribed to polyphenols, although their therapeutic relevance when resistance has developed is not clear. The present study evaluated the anti-tumor potential of polyphenol-rich olive mill wastewater (OMWW) on chemo-sensitive and cisplatin- and gemcitabine-resistant T24, RT112, and TCCSUP bladder cancer cells in vitro. The cells were treated with different dilutions of OMWW, and tumor growth and clone formation were evaluated. Possible mechanisms of action were investigated by evaluating cell cycle phases and cell cycle-regulating proteins. OMWW profoundly inhibited the growth and proliferation of chemo-sensitive as well as gemcitabine- and cisplatin-resistant bladder cancer cells. Depending on the cell line and on gemcitabine- or cisplatin-resistance, OMWW induced cell cycle arrest at different phases. These differing phase arrests were accompanied by differing alterations in the CDK-cyclin axis. Considerable suppression of the Akt-mTOR pathway by OMWW was observed in all three cell lines. Since OMWW blocks the cell cycle through the manipulation of the cyclin-CDK axis and the deactivation of Akt-mTOR signaling, OMWW could become relevant in supporting bladder cancer therapy.
KW  - olive mill wastewater (OMWW)
KW  - bladder cancer
KW  - tumor growth
KW  - Akt-mTOR signaling
KW  - CDK-cyclin axis
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/79551
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-795510
SN  - 2072-6643
N1  - This research was funded by Fattoria La Vialla, Castiglion Fibocchi, Italy, and by the Brigitta & Norbert Muth Stiftung, Wiesbaden, Germany.
VL  - 14
IS  - 2, art. 369
SP  - 1
EP  - 14
PB  - MDPI
CY  - Basel
ER  -