4.7 Article

Crosstalk between β2-and α2-Adrenergic Receptors in the Regulation of B16F10 Melanoma Cell Proliferation

Journal

Publisher

MDPI
DOI: 10.3390/ijms23094634

Keywords

cyclic AMP; beta 2-adrenergic receptors; alpha 2-adrenergic receptors; proliferation; melanoma

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This study found that beta-AR stimulation affects the proliferative activity of B16F10 cells by regulating cAMP levels. Additionally, alpha 2-AR agonists can inhibit cell proliferation, which is disrupted by the inhibitory effect of beta-AR agonists on alpha 2-AR. These findings suggest that the crosstalk between beta-AR and alpha 2-AR signaling pathways plays an important role in regulating melanoma 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 beta-AR stimulation affects the antiproliferative action of alpha 2-AR agonists on B16F10 cells and, if so, to determine the relative contribution of beta-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 beta-AR agonist, increased cAMP levels in B16F10 melanoma cells without affecting cell proliferation. Propranolol inhibited the cAMP response to isoproterenol. In addition, stimulation of alpha 2-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 beta 2-AR antagonist, or propranolol, suggesting that isoproterenol effects are mainly mediated by the beta 2-AR stimulation. We conclude that the crosstalk between the beta 2-AR and alpha 2-AR signaling pathways regulates the proliferative activity of B16F10 cells and may therefore represent a therapeutic target for melanoma therapy.

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