Agonist Effects of Propranolol on Non-Tumor Human Breast Cells

Abstract

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.

β2-Adrenoceptor Activation Favor Acquisition of Tumorigenic Properties in Non-Tumorigenic MCF-10A Breast Epithelial Cells

“…The present study corroborates that treatments that promote MET also impair lamellipodia and filopodia formation, in line with the evidence available [71]. Moreover, there is evidence that the activation of β-adrenoceptors can lead to an inhibition of cell protrusions formation (bronchial [72], keratinocytes [73,74], and breast [75] non-tumorigenic cells). In the current study, the impairment of lamellipodia and filopodia formation was observed after treatment with all adrenoceptor agonists tested (isoprenaline, adrenaline and salbutamol) in concentration range with affinity to β-adrenoceptors.…”

“…Studies on the role of β-adrenoceptors in cell migration have shown that these receptors can either mediate stimulatory or inhibitory effects on cell migration, depending on the cell type and model used [27,79]. An adrenoceptor-mediated decrease in cell migration was previously shown to occur in non-tumorigenic cells from the bronchi [72], skin [73,74], breast [75], and cornea [80], and in cancer models of the mouth [81], breast [82], prostate [70], and melanoma [79].…”

The stimulation and inhibition of beta-2 adrenergic receptor on the inflammatory responses of ovary and immune system in the aged laying hens

“…Although BAA and BB benefit from β2ADR signaling pathway with the contradictory functions, they approximately demonstrated the similar results, in particular mRNA expressions of β2ADR, anti-, and pro-inflammatory cytokines. In this regard, Gargiulo et al clarified the fact that several BB do not really act as pure antagonists and some of them show the same final action to their agonists through the different or similar mechanisms [ 46 ]. Additionally, Sozzani et al suggested that the effect of Propranolol at high doses is not mediated by β2ADR but by its membrane stabilizer properties [ 47 ].…”

Cross‐talk of cholinergic and β‐adrenergic receptor signalling in chronic myeloid leukemia K562 cells

“…Liao et al 48 showed that propranolol at 50 μM concentration did not cause apoptosis of gastric adenocarcinoma BGC‐823 and SGC‐7901cell lines. Gargiulo et al 49 showed that IPN and propranolol caused a significant decrease in ‘in vitro cell proliferation of MCF‐7 and MCF‐10A cells’. They described that the non‐selective antagonist propranolol behaved as an agonist in the non‐tumour line MCF‐10A through different mechanisms, namely by increasing the adhesion and decreasing the proliferation via the β 2 ‐ARs.…”