Artículo
Agonist Effects of Propranolol on Non-Tumor Human Breast Cells
Gargiulo, Lucía
; Rivero, Ezequiel Mariano
; Di Siervi, Nicolás
; Buzzi, Edgardo David
; Buffone, Mariano Gabriel
; Davio, Carlos Alberto
; Luthy, Isabel Alicia
; Bruzzone, Ariana
Fecha de publicación:
22/04/2020
Editorial:
MDPI
Revista:
Cells
ISSN:
2073-4409
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The β-blocker propranolol (PROP) has been proposed as a repurposed treatment for breast cancer. The similarity of action between β-agonists and antagonists found on breast cells encouraged us to compare PROP and isoproterenol (ISO, agonist) signaling pathways on a human breast cell line. Cell proliferation was measured by cell counting and DNA-synthesis. Cell adhesion was measured counting the cells that remained adhered to the plastic after different treatments. Changes in actin cytoskeleton were observed by fluorescence staining and Western Blot. ISO and PROP caused a diminution of cell proliferation and an increase of cell adhesion, reverted by the pure β-antagonist ICI-118551. ISO and PROP induced a reorganization of actin cytoskeleton increasing F-actin, p-COFILIN and p-LIMK. While ISO elicited a marked enhancement of cAMP concentrations and an increase of vasodilator-stimulated phosphoprotein (VASP) and cAMP response element-binding protein (CREB) phosphorylation, PROP did not. Clathrin-mediated endocytosis inhibition or β-arrestin1 dominant-negative mutant abrogated PROP-induced cell adhesion and COFILIN phosphorylation. The fact that PROP has been proposed as an adjuvant drug for breast cancer makes it necessary to determine the specific action of PROP in breast models. These results provide an explanation for the discrepancies observed between experimental results and clinical evidence.
Palabras clave:
PROPRANOLOL
,
BIASED AGONIST
,
CELL ADHESION
,
MCF-10A
,
β-BLOCKER
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(INIBIBB)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Articulos(ININFA)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
Citación
Gargiulo, Lucía; Rivero, Ezequiel Mariano; Di Siervi, Nicolás; Buzzi, Edgardo David; Buffone, Mariano Gabriel; et al.; Agonist Effects of Propranolol on Non-Tumor Human Breast Cells; MDPI; Cells; 9; 4; 22-4-2020; 1036-1050
Compartir
Altmétricas