A2b adenosine receptor agonist induces cell cycle arrest and apoptosis in breast cancer stem cells via modulation of ERK1/2 phosphorylation

Introduction & Aim: Cancer stem cells (CSCs) have a crucial role in recurrence and metastasis of breast cancer. Targeting these cells is critical for effective treatment of breast cancer. The function of a2b adenosine receptor in breast CSCs is still not elucidated; the aim of this study was to investigate the role and molecular mechanisms of A2BAR in breast CSCs. Methods: Antiproliferative effect of A2B adenosine receptor (BAY 60-6583) was evaluated by MTS assay. Cell cycle and cell apoptosis effects of adenosine were measured by flow cytometry. The expression levels of cell cycle and apoptotice regulatory proteins as well as ERK1/2 were analysed by western blotting. Results: A2bAR agonist reduces CSCs population and mammosphere formation in breast CSCs. Activation of A2bAR induces G1 cell cycle arrest in breast CSCs in conjunction with a marked down- of cyclin D1 and cdk4. Stimulation of A2bAR induces apoptosis by regulation of bax/bcl-2 ratio. Moreover, A2bAR agonist inhibited ERK1/2 phosphorylation Conclusions: These findings indicated that activation of A2bAR induces cell cycle arrest and apoptosis through inhibition of ERK1/2 pathways in breast CSCs