Activation of ß2-adrenergic receptor by (R,R')-4'-methoxy-1-naphthylfenoterol inhibits proliferation and motility of melanoma cells.
Cell Signal
; 27(5): 997-1007, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25703025
ABSTRACT
(R,R')-4'-methoxy-1-naphthylfenoterol [(R,R')-MNF] is a highly-selective ß2 adrenergic receptor (ß2-AR) agonist. Incubation of a panel of human-derived melanoma cell lines with (R,R')-MNF resulted in a dose- and time-dependent inhibition of motility as assessed by in vitro wound healing and xCELLigence migration and invasion assays. Activity of (R,R')-MNF positively correlated with the ß2-AR expression levels across tested cell lines. The anti-motility activity of (R,R')-MNF was inhibited by the ß2-AR antagonist ICI-118,551 and the protein kinase A inhibitor H-89. The adenylyl cyclase activator forskolin and the phosphodiesterase 4 inhibitor Ro 20-1724 mimicked the ability of (R,R')-MNF to inhibit migration of melanoma cell lines in culture, highlighting the importance of cAMP for this phenomenon. (R,R')-MNF caused significant inhibition of cell growth in ß2-AR-expressing cells as monitored by radiolabeled thymidine incorporation and xCELLigence system. The MEK/ERK cascade functions in cellular proliferation, and constitutive phosphorylation of MEK and ERK at their active sites was significantly reduced upon ß2-AR activation with (R,R')-MNF. Protein synthesis was inhibited concomitantly both with increased eEF2 phosphorylation and lower expression of tumor cell regulators, EGF receptors, cyclin A and MMP-9. Taken together, these results identified ß2-AR as a novel potential target for melanoma management, and (R,R')-MNF as an efficient trigger of anti-tumorigenic cAMP/PKA-dependent signaling in ß2-AR-expressing lesions.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
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Receptores Adrenérgicos beta 2
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Proliferação de Células
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Fenoterol
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Agonistas de Receptores Adrenérgicos beta 2
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Melanoma
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Cell Signal
Ano de publicação:
2015
Tipo de documento:
Article