Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways

Physiologically, beta-adrenoceptors are major regulators of lipid metabolism, which may be reflected in alterations in lipid droplet dynamics. beta-adrenoceptors have also been shown to participate in breast cancer carcinogenesis. Since lipid droplets may be seen as a hallmark of cancer, the present study aimed to investigate the role of beta-adrenoceptors in the regulation of lipid droplet dynamics in MCF-7 breast cancer cells. Cells were treated for up to 72 h with adrenaline (an endogenous adrenoceptor agonist), isoprenaline (a non-selective beta-adrenoceptor agonist) and salbutamol (a selective beta(2)-selective agonist), and their effects on lipid droplets were evaluated using Nile Red staining. Adrenaline or isoprenaline, but not salbutamol, caused a lipid-accumulating phenotype in the MCF-7 cells. These effects were significantly reduced by selective beta(1)- and beta(3)-antagonists (10 nM atenolol and 100 nM L-748,337, respectively), indicating a dependence on both beta(1)- and beta(3)-adrenoceptors. These effects were dependent on the cAMP signalling pathway, involving both protein kinase A (PKA) and cAMP-dependent guanine-nucleotide-exchange (EPAC) proteins: treatment with cAMP-elevating agents (forskolin or 8-Br-cAMP) induced lipid droplet accumulation, whereas either 1 mu M H-89 or 1 mu M ESI-09 (PKA or EPAC inhibitors, respectively) abrogated this effect. Taken together, the present results demonstrate the existence of a beta-adrenoceptor-mediated regulation of lipid droplet dynamics in breast cancer cells, likely involving beta(1)- and beta(3)-adrenoceptors, revealing a new mechanism by which adrenergic stimulation may influence cancer cell metabolism.

Automated summary

Beta-adrenoceptors play a role in the regulation of lipid droplet dynamics in breast cancer cells, and their activation can lead to lipid accumulation. This effect is dependent on beta(1)- and beta(3)-adrenoceptors, as well as the cAMP signaling pathway.