Crosstalk between β2- and α2-Adrenergic Receptors in the Regulation of B16F10 Melanoma Cell Proliferation
Adrenergic receptors (AR) belong to the G protein-coupled receptor superfamily and regulate migration and proliferation in various cell types. The objective of this study was to evaluate whether β-AR stimulation affects the antiproliferative action of α2-AR agonists on B16F10 cells and, if so, to de...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/4634 |
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| author | Paola Matarrese Sonia Maccari Barbara Ascione Rosa Vona Vanessa Vezzi Tonino Stati Maria Cristina Grò Giuseppe Marano Caterina Ambrosio Paola Molinari |
| author_facet | Paola Matarrese Sonia Maccari Barbara Ascione Rosa Vona Vanessa Vezzi Tonino Stati Maria Cristina Grò Giuseppe Marano Caterina Ambrosio Paola Molinari |
| author_sort | Paola Matarrese |
| collection | DOAJ |
| description | Adrenergic receptors (AR) belong to the G protein-coupled receptor superfamily and regulate migration and proliferation in various cell types. The objective of this study was to evaluate whether β-AR stimulation affects the antiproliferative action of α2-AR agonists on B16F10 cells and, if so, to determine the relative contribution of β-AR subtypes. Using pharmacological approaches, evaluation of Ki-67 expression by flow cytometry and luciferase-based cAMP assay, we found that treatment with isoproterenol, a β-AR agonist, increased cAMP levels in B16F10 melanoma cells without affecting cell proliferation. Propranolol inhibited the cAMP response to isoproterenol. In addition, stimulation of α2-ARs with agonists such as clonidine, a well-known antihypertensive drug, decreased cancer cell proliferation. This effect on cell proliferation was suppressed by treatment with isoproterenol. In turn, the suppressive effects of isoproterenol were abolished by the treatment with either ICI 118,551, a β2-AR antagonist, or propranolol, suggesting that isoproterenol effects are mainly mediated by the β2-AR stimulation. We conclude that the crosstalk between the β2-AR and α2-AR signaling pathways regulates the proliferative activity of B16F10 cells and may therefore represent a therapeutic target for melanoma therapy. |
| first_indexed | 2024-03-10T04:07:40Z |
| format | Article |
| id | doaj.art-df82fdb5311844edbdb09b3eaf4b68c3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:07:40Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-df82fdb5311844edbdb09b3eaf4b68c32023-11-23T08:20:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239463410.3390/ijms23094634Crosstalk between β2- and α2-Adrenergic Receptors in the Regulation of B16F10 Melanoma Cell ProliferationPaola Matarrese0Sonia Maccari1Barbara Ascione2Rosa Vona3Vanessa Vezzi4Tonino Stati5Maria Cristina Grò6Giuseppe Marano7Caterina Ambrosio8Paola Molinari9Center for Gender-Specific Medicine, National Institute of Health, Viale Regina Elena 299, 00161 Rome, ItalyCenter for Gender-Specific Medicine, National Institute of Health, Viale Regina Elena 299, 00161 Rome, ItalyCenter for Gender-Specific Medicine, National Institute of Health, Viale Regina Elena 299, 00161 Rome, ItalyCenter for Gender-Specific Medicine, National Institute of Health, Viale Regina Elena 299, 00161 Rome, ItalyNational Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, ItalyCenter for Gender-Specific Medicine, National Institute of Health, Viale Regina Elena 299, 00161 Rome, ItalyNational Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, ItalyCenter for Gender-Specific Medicine, National Institute of Health, Viale Regina Elena 299, 00161 Rome, ItalyNational Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, ItalyNational Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, ItalyAdrenergic receptors (AR) belong to the G protein-coupled receptor superfamily and regulate migration and proliferation in various cell types. The objective of this study was to evaluate whether β-AR stimulation affects the antiproliferative action of α2-AR agonists on B16F10 cells and, if so, to determine the relative contribution of β-AR subtypes. Using pharmacological approaches, evaluation of Ki-67 expression by flow cytometry and luciferase-based cAMP assay, we found that treatment with isoproterenol, a β-AR agonist, increased cAMP levels in B16F10 melanoma cells without affecting cell proliferation. Propranolol inhibited the cAMP response to isoproterenol. In addition, stimulation of α2-ARs with agonists such as clonidine, a well-known antihypertensive drug, decreased cancer cell proliferation. This effect on cell proliferation was suppressed by treatment with isoproterenol. In turn, the suppressive effects of isoproterenol were abolished by the treatment with either ICI 118,551, a β2-AR antagonist, or propranolol, suggesting that isoproterenol effects are mainly mediated by the β2-AR stimulation. We conclude that the crosstalk between the β2-AR and α2-AR signaling pathways regulates the proliferative activity of B16F10 cells and may therefore represent a therapeutic target for melanoma therapy.https://www.mdpi.com/1422-0067/23/9/4634cyclic AMPβ2-adrenergic receptorsα2-adrenergic receptorsproliferationmelanoma |
| spellingShingle | Paola Matarrese Sonia Maccari Barbara Ascione Rosa Vona Vanessa Vezzi Tonino Stati Maria Cristina Grò Giuseppe Marano Caterina Ambrosio Paola Molinari Crosstalk between β2- and α2-Adrenergic Receptors in the Regulation of B16F10 Melanoma Cell Proliferation International Journal of Molecular Sciences cyclic AMP β2-adrenergic receptors α2-adrenergic receptors proliferation melanoma |
| title | Crosstalk between β2- and α2-Adrenergic Receptors in the Regulation of B16F10 Melanoma Cell Proliferation |
| title_full | Crosstalk between β2- and α2-Adrenergic Receptors in the Regulation of B16F10 Melanoma Cell Proliferation |
| title_fullStr | Crosstalk between β2- and α2-Adrenergic Receptors in the Regulation of B16F10 Melanoma Cell Proliferation |
| title_full_unstemmed | Crosstalk between β2- and α2-Adrenergic Receptors in the Regulation of B16F10 Melanoma Cell Proliferation |
| title_short | Crosstalk between β2- and α2-Adrenergic Receptors in the Regulation of B16F10 Melanoma Cell Proliferation |
| title_sort | crosstalk between β2 and α2 adrenergic receptors in the regulation of b16f10 melanoma cell proliferation |
| topic | cyclic AMP β2-adrenergic receptors α2-adrenergic receptors proliferation melanoma |
| url | https://www.mdpi.com/1422-0067/23/9/4634 |
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