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

Abstract

Physiologically, β-adrenoceptors are major regulators of lipid metabolism, which may be reflected in alterations in lipid droplet dynamics. β-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 β-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 β-adrenoceptor agonist) and salbutamol (a selective β2-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 β1- and β3-antagonists (10 nM atenolol and 100 nM L-748,337, respectively), indicating a dependence on both β1- and β3-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 µM H-89 or 1 µM ESI-09 (PKA or EPAC inhibitors, respectively) abrogated this effect. Taken together, the present results demonstrate the existence of a β-adrenoceptor-mediated regulation of lipid droplet dynamics in breast cancer cells, likely involving β1- and β3-adrenoceptors, revealing a new mechanism by which adrenergic stimulation may influence cancer cell metabolism.

• Authors: Dany Silva, Katarzyna Kacprzak, Clara Quintas, Jorge Gonçalves, Paula Fresco
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 1 (Jan 01 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36614209 (Publication Type: Journal Article)

Chemical References

• Isoproterenol
• Cyclic AMP-Dependent Protein Kinases
• Adrenergic beta-Agonists
• Receptors, Adrenergic, beta
• Albuterol
• Epinephrine
• Guanine Nucleotide Exchange Factors
• Adrenergic beta-Antagonists

Topics

• Humans
• Isoproterenol (pharmacology)
• Lipid Droplets
• MCF-7 Cells
• Cyclic AMP-Dependent Protein Kinases
• Adrenergic beta-Agonists (pharmacology)
• Receptors, Adrenergic, beta
• Albuterol (pharmacology)
• Epinephrine
• Guanine Nucleotide Exchange Factors
• Adrenergic beta-Antagonists (pharmacology)
• Neoplasms