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...
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MDPI AG
2022-01-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/2/369 |
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| author | Jochen Rutz Sebastian Maxeiner Eva Juengel Felix K.-H. Chun Igor Tsaur Roman A. Blaheta |
| author_facet | Jochen Rutz Sebastian Maxeiner Eva Juengel Felix K.-H. Chun Igor Tsaur Roman A. Blaheta |
| author_sort | Jochen Rutz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T00:46:52Z |
| format | Article |
| id | doaj.art-3a917d807fb246ff87affe9eba1fb773 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T00:46:52Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-3a917d807fb246ff87affe9eba1fb7732023-11-23T14:58:20ZengMDPI AGNutrients2072-66432022-01-0114236910.3390/nu14020369Olive Mill Wastewater Inhibits Growth and Proliferation of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro by Down-Regulating the Akt/mTOR-Signaling PathwayJochen Rutz0Sebastian Maxeiner1Eva Juengel2Felix K.-H. Chun3Igor Tsaur4Roman A. Blaheta5Department of Urology, Goethe-University, 60590 Frankfurt am Main, GermanyDepartment of Urology, Goethe-University, 60590 Frankfurt am Main, GermanyDepartment of Urology and Pediatric Urology, University Medicine Mainz, 55131 Mainz, GermanyDepartment of Urology, Goethe-University, 60590 Frankfurt am Main, GermanyDepartment of Urology and Pediatric Urology, University Medicine Mainz, 55131 Mainz, GermanyDepartment of Urology, Goethe-University, 60590 Frankfurt am Main, GermanyBladder 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.https://www.mdpi.com/2072-6643/14/2/369olive mill wastewater (OMWW)bladder cancertumor growthAkt-mTOR signalingCDK-cyclin axis |
| spellingShingle | Jochen Rutz Sebastian Maxeiner Eva Juengel Felix K.-H. Chun Igor Tsaur Roman A. Blaheta 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 Nutrients olive mill wastewater (OMWW) bladder cancer tumor growth Akt-mTOR signaling CDK-cyclin axis |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | olive mill wastewater (OMWW) bladder cancer tumor growth Akt-mTOR signaling CDK-cyclin axis |
| url | https://www.mdpi.com/2072-6643/14/2/369 |
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