دورية أكاديمية
Blockade of ß-Adrenergic Receptors by Nebivolol Enables Tumor Control Potential for Uveal Melanoma in 3D Tumor Spheroids and 2D Cultures.
العنوان: | Blockade of ß-Adrenergic Receptors by Nebivolol Enables Tumor Control Potential for Uveal Melanoma in 3D Tumor Spheroids and 2D Cultures. |
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المؤلفون: | Farhoumand LS; Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Liu H; Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Tsimpaki T; Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Hendgen-Cotta UB; CardioScience Labs, Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Rassaf T; CardioScience Labs, Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Bechrakis NE; Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Fiorentzis M; Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany., Berchner-Pfannschmidt U; Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany. |
المصدر: | International journal of molecular sciences [Int J Mol Sci] 2023 Mar 20; Vol. 24 (6). Date of Electronic Publication: 2023 Mar 20. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
مواضيع طبية MeSH: | Ethanolamines*/pharmacology , Melanoma*/drug therapy, Adult ; Humans ; Nebivolol/pharmacology ; Benzopyrans/pharmacology ; Adrenergic beta-Antagonists/pharmacology ; Receptors, Adrenergic, beta |
مستخلص: | Uveal melanoma (UM) is the most common primary cancer of the eye in adults. A new systemic therapy is needed to reduce the high metastasis and mortality rate. As β-blockers are known to have anti-tumor effects on various cancer entities, this study focuses on investigating the effect of β1-selective blockers atenolol, celiprolol, bisoprolol, metoprolol, esmolol, betaxolol, and in particular, nebivolol on UM. The study was performed on 3D tumor spheroids as well as 2D cell cultures, testing tumor viability, morphological changes, long-term survival, and apoptosis. Flow cytometry revealed the presence of all three β-adrenoceptors with a dominance of β2-receptors on cell surfaces. Among the blockers tested, solely nebivolol concentration-dependently decreased viability and altered 3D tumor spheroid structure. Nebivolol blocked the repopulation of cells spreading from 3D tumor spheroids, indicating a tumor control potential at a concentration of ≥20 µM. Mechanistically, nebivolol induced ATP depletion and caspase-3/7 activity, indicating that mitochondria-dependent signaling is involved. D-nebivolol or nebivolol combined with the β2-antagonist ICI 118.551 displayed the highest anti-tumor effects, suggesting a contribution of both β1- and β2-receptors. Thus, the present study reveals the tumor control potential of nebivolol in UM, which may offer a perspective for co-adjuvant therapy to reduce recurrence or metastasis. |
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معلومات مُعتمدة: | ELAN 2023 Essen Laboratory and Science Training Program for Young Physicians; CSC 2023 Chinese Scholarship Fund |
فهرسة مساهمة: | Keywords: 3D tumor spheroids; anti-tumor activity; nebivolol; tumor control potential; uveal melanoma; ß1-selective blocker |
المشرفين على المادة: | 030Y90569U (Nebivolol) 0 (Ethanolamines) 0 (Benzopyrans) 0 (Adrenergic beta-Antagonists) 0 (Receptors, Adrenergic, beta) |
SCR Disease Name: | Uveal melanoma |
تواريخ الأحداث: | Date Created: 20230329 Date Completed: 20230330 Latest Revision: 20230331 |
رمز التحديث: | 20230331 |
مُعرف محوري في PubMed: | PMC10054088 |
DOI: | 10.3390/ijms24065894 |
PMID: | 36982966 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1422-0067 |
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DOI: | 10.3390/ijms24065894 |