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

  • 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.

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Author:Jochen RutzGND, Sebastian MaxeinerGND, Eva JüngelORCiDGND, Felix ChunORCiDGND, Igor TsaurORCiDGND, Roman A. BlahetaORCiD
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/35057550
Parent Title (English):Nutrients
Place of publication:Basel
Document Type:Article
Date of Publication (online):2022/01/15
Date of first Publication:2022/01/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/11/16
Tag:Akt-mTOR signaling; CDK-cyclin axis; bladder cancer; olive mill wastewater (OMWW); tumor growth
Issue:2, art. 369
Article Number:369
Page Number:14
First Page:1
Last Page:14
This research was funded by Fattoria La Vialla, Castiglion Fibocchi, Italy, and by the Brigitta & Norbert Muth Stiftung, Wiesbaden, Germany.
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International