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; LÜTHY, ISABEL ALICIA; BRUZZONE, ARIANA

Cells

MDPI

Lugar: Basel; Año: 2020 vol. 9 p. 1 - 14

The beta-blocker propranolol (PROP) has been proposed as a repurposed treatment for breast cancer. The similarity of action between -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 beta-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 beta-arrestin1 dominant-negative mutant abrogated PROP-induced cell adhesion and COFILIN phosphorylation. The fact that PROPhas 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.