The Adrenergic Receptor Antagonist Carvedilol Elicits Anti-Tumor Responses in Uveal Melanoma 3D Tumor Spheroids and May Serve as Co-Adjuvant Therapy with Radiation
| Autor: | Lina S. Farhoumand, Miltiadis Fiorentzis, Miriam M. Kraemer, Ali Sak, Martin Stuschke, Tienush Rassaf, Ulrike Hendgen-Cotta, Nikolaos E. Bechrakis, Utta Berchner-Pfannschmidt |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Cancer Research
Oncology embryonic structures Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Augenheilkunde Medizin uveal melanoma adrenergic receptor blocker carvedilol anti-tumor potential co-adjuvant treatment radiation uveal melanoma -- adrenergic receptor blocker -- carvedilol -- anti-tumor potential -- co-adjuvant treatment -- radiation ddc:610 Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Strahlentherapie Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Kardiologie und Angiologie |
| Zdroj: | Cancers; Volume 14; Issue 13; Pages: 3097 |
| Popis: | Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite local tumor control, no effective therapy has been found to prevent metastasis, resulting in a high mortality rate. In the present study, we evaluated the anti-tumor potential of non-selective ß-blockers in 3D tumor spheroids grown from UM cell lines. Of the various ß-blockers tested, carvedilol and its enantiomers were most potent in decreasing the viability of Mel270 spheroids. Carvedilol at a concentration of 10–50 µM significantly elicited cytotoxicity and induced apoptosis in spheroid cells. In result, carvedilol inhibited tumor spheroid growth and compactness, and furthermore prevented the long-term survival and repopulation of spreading spheroid cells. The drug sensitivity of the different spheroids grown from Mel270, 92-1, UPMD2, or UPMM3 cell lines was dependent on 3D morphology rather than on high-risk cytogenetic profile or adrenergic receptor expression levels. In fact, the monosomy-3-containing UPMM3 cell line was most responsive to carvedilol treatment compared to the other cell lines. The concurrent treatment of UPMM3 spheroids with carvedilol and 5 or 10 Gy irradiation revealed additive cytotoxic effects that provided tumor control. Collectively, our data demonstrate the anti-tumor properties of carvedilol and its enantiomers, which may serve as candidates for the co-adjuvant therapy of UM. |
| Databáze: | OpenAIRE |
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