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.

Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI Publishing

Cell Proliferation/*drug effects ; Drug Resistance, Neoplasm/*drug effects ; Olea/*chemistry ; Polyphenols/*pharmacology ; Urinary Bladder Neoplasms/*drug therapy ; Wastewater/*chemistry; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cisplatin/pharmacology ; Cyclin-Dependent Kinases/metabolism ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Humans ; Polyphenols/analysis ; Proto-Oncogene Proteins c-akt/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Urinary Bladder Neoplasms/metabolism ; Urinary Bladder Neoplasms/pathology ; Gemcitabine

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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N/A Fattoria La Vialla, Castiglion Fibocchi, Italy; N/A Brigitta & Norbert Muth Stiftung, Wiesbaden, Germany

Keywords: Akt-mTOR signaling; CDK-cyclin axis; bladder cancer; olive mill wastewater (OMWW); tumor growth

0 (Antineoplastic Agents)
0 (Polyphenols)
0 (Waste Water)
0W860991D6 (Deoxycytidine)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
EC 2.7.11.22 (Cyclin-Dependent Kinases)
Q20Q21Q62J (Cisplatin)
0 (Gemcitabine)

Date Created: 20220121 Date Completed: 20220126 Latest Revision: 20221207

20221213

PMC8778865

10.3390/nu14020369

35057550