Adenosine A3 receptor antagonists as anti‐tumor treatment in human prostate cancer: an in vitro study
Prostate cancer (PCa) is one of the most common cancers in men, and for patients with PCa that cannot be surgically resected or treated, androgen suppression therapy often results in significant adverse effects. Recent studies have shown that A3 adenosine receptors (A3ARs) are overexpressed in prost...
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| Format: | Article |
| Language: | English |
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Wiley
2025-07-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.70024 |
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| author | Maria Beatrice Morelli Andrea Spinaci Cui Chang Rosaria Volpini Catia Lambertucci Matteo Landriscina Vincenza Conteduca Consuelo Amantini Cristina Aguzzi Laura Zeppa Martina Giangrossi Laura Soverchia Matteo Santoni Massimo Nabissi Giorgio Santoni Carlo Polidori |
| author_facet | Maria Beatrice Morelli Andrea Spinaci Cui Chang Rosaria Volpini Catia Lambertucci Matteo Landriscina Vincenza Conteduca Consuelo Amantini Cristina Aguzzi Laura Zeppa Martina Giangrossi Laura Soverchia Matteo Santoni Massimo Nabissi Giorgio Santoni Carlo Polidori |
| author_sort | Maria Beatrice Morelli |
| collection | DOAJ |
| description | Prostate cancer (PCa) is one of the most common cancers in men, and for patients with PCa that cannot be surgically resected or treated, androgen suppression therapy often results in significant adverse effects. Recent studies have shown that A3 adenosine receptors (A3ARs) are overexpressed in prostate cancer (PCa), and several A3AR agonists and antagonists have been investigated as potential anticancer drugs. In this study, we investigated the potential therapeutic effects of the A3AR antagonists AR 292 and AR 357 in human PCa cell lines. LNCaP, DU‐145, and PC3 cell lines were treated with AR 292 and AR 357 compounds, and their cytotoxic effects were determined using viability assays, flow cytometry, and western blotting. Moreover, the drug transporter gene profile was evaluated using RT‐PCR in untreated and A3AR antagonist‐treated PCa cells. Both AR 292 and AR 357 showed antiproliferative effects with significant cell cycle arrest and induced DNA damage leading to cell death. AR 292 and especially AR 357 modulated the expression of drug transporter genes involved in chemoresistance, ferroptosis, and the hypoxia response. Ferroptosis was induced in DU‐145 cells treated with both compounds as well as in PC3 cells treated with AR 357. However, the treatment of PC3 cells with AR 292 and the treatment of LNCaP cells with both AR 292 and AR 357 resulted in necrotic cell death. In conclusion, our study showed that A3AR ligands exert anticancer effects via different mechanisms on PCa cell lines through the activation of multiple molecular pathways. |
| format | Article |
| id | doaj-art-1edd8542d2f04fc58e87a3701954f97d |
| institution | DOAJ |
| issn | 2211-5463 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-1edd8542d2f04fc58e87a3701954f97d2025-08-20T03:16:07ZengWileyFEBS Open Bio2211-54632025-07-011571159117510.1002/2211-5463.70024Adenosine A3 receptor antagonists as anti‐tumor treatment in human prostate cancer: an in vitro studyMaria Beatrice Morelli0Andrea Spinaci1Cui Chang2Rosaria Volpini3Catia Lambertucci4Matteo Landriscina5Vincenza Conteduca6Consuelo Amantini7Cristina Aguzzi8Laura Zeppa9Martina Giangrossi10Laura Soverchia11Matteo Santoni12Massimo Nabissi13Giorgio Santoni14Carlo Polidori15Experimental Medicine Unit School of Pharmacy, University of Camerino ItalyMedicinal Chemistry Unit School of Pharmacy, University of Camerino ItalyMedicinal Chemistry Unit School of Pharmacy, University of Camerino ItalyMedicinal Chemistry Unit School of Pharmacy, University of Camerino ItalyMedicinal Chemistry Unit School of Pharmacy, University of Camerino ItalyUnit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences – Ospedali Riuniti University of Foggia Foggia ItalyUnit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences – Ospedali Riuniti University of Foggia Foggia ItalySchool of Bioscience and Veterinary Medicine University of Camerino ItalyExperimental Medicine Unit School of Pharmacy, University of Camerino ItalySchool of Bioscience and Veterinary Medicine University of Camerino ItalyExperimental Medicine Unit School of Pharmacy, University of Camerino ItalyExperimental Medicine Unit School of Pharmacy, University of Camerino ItalyOncology Unit Macerata Hospital Macerata ItalyExperimental Medicine Unit School of Pharmacy, University of Camerino ItalyExperimental Medicine Unit School of Pharmacy, University of Camerino ItalyExperimental Medicine Unit School of Pharmacy, University of Camerino ItalyProstate cancer (PCa) is one of the most common cancers in men, and for patients with PCa that cannot be surgically resected or treated, androgen suppression therapy often results in significant adverse effects. Recent studies have shown that A3 adenosine receptors (A3ARs) are overexpressed in prostate cancer (PCa), and several A3AR agonists and antagonists have been investigated as potential anticancer drugs. In this study, we investigated the potential therapeutic effects of the A3AR antagonists AR 292 and AR 357 in human PCa cell lines. LNCaP, DU‐145, and PC3 cell lines were treated with AR 292 and AR 357 compounds, and their cytotoxic effects were determined using viability assays, flow cytometry, and western blotting. Moreover, the drug transporter gene profile was evaluated using RT‐PCR in untreated and A3AR antagonist‐treated PCa cells. Both AR 292 and AR 357 showed antiproliferative effects with significant cell cycle arrest and induced DNA damage leading to cell death. AR 292 and especially AR 357 modulated the expression of drug transporter genes involved in chemoresistance, ferroptosis, and the hypoxia response. Ferroptosis was induced in DU‐145 cells treated with both compounds as well as in PC3 cells treated with AR 357. However, the treatment of PC3 cells with AR 292 and the treatment of LNCaP cells with both AR 292 and AR 357 resulted in necrotic cell death. In conclusion, our study showed that A3AR ligands exert anticancer effects via different mechanisms on PCa cell lines through the activation of multiple molecular pathways.https://doi.org/10.1002/2211-5463.70024adenosineadenosine receptor antagonistschemotherapyPC3 cell lineprostate cancer |
| spellingShingle | Maria Beatrice Morelli Andrea Spinaci Cui Chang Rosaria Volpini Catia Lambertucci Matteo Landriscina Vincenza Conteduca Consuelo Amantini Cristina Aguzzi Laura Zeppa Martina Giangrossi Laura Soverchia Matteo Santoni Massimo Nabissi Giorgio Santoni Carlo Polidori Adenosine A3 receptor antagonists as anti‐tumor treatment in human prostate cancer: an in vitro study FEBS Open Bio adenosine adenosine receptor antagonists chemotherapy PC3 cell line prostate cancer |
| title | Adenosine A3 receptor antagonists as anti‐tumor treatment in human prostate cancer: an in vitro study |
| title_full | Adenosine A3 receptor antagonists as anti‐tumor treatment in human prostate cancer: an in vitro study |
| title_fullStr | Adenosine A3 receptor antagonists as anti‐tumor treatment in human prostate cancer: an in vitro study |
| title_full_unstemmed | Adenosine A3 receptor antagonists as anti‐tumor treatment in human prostate cancer: an in vitro study |
| title_short | Adenosine A3 receptor antagonists as anti‐tumor treatment in human prostate cancer: an in vitro study |
| title_sort | adenosine a3 receptor antagonists as anti tumor treatment in human prostate cancer an in vitro study |
| topic | adenosine adenosine receptor antagonists chemotherapy PC3 cell line prostate cancer |
| url | https://doi.org/10.1002/2211-5463.70024 |
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