Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways
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...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/767 |
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| author | Dany Silva Katarzyna Kacprzak Clara Quintas Jorge Gonçalves Paula Fresco |
| author_facet | Dany Silva Katarzyna Kacprzak Clara Quintas Jorge Gonçalves Paula Fresco |
| author_sort | Dany Silva |
| collection | DOAJ |
| description | 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 β<sub>2</sub>-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 β<sub>1</sub>- and β<sub>3</sub>-antagonists (10 nM atenolol and 100 nM L-748,337, respectively), indicating a dependence on both β<sub>1</sub>- and β<sub>3</sub>-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 β<sub>1</sub>- and β<sub>3</sub>-adrenoceptors, revealing a new mechanism by which adrenergic stimulation may influence cancer cell metabolism. |
| first_indexed | 2024-03-11T09:58:10Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:58:10Z |
| publishDate | 2023-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b6a54fca3e6a48a7a181f7b0074e02552023-11-16T15:38:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124176710.3390/ijms24010767Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC PathwaysDany Silva0Katarzyna Kacprzak1Clara Quintas2Jorge Gonçalves3Paula Fresco4Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalLaboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalLaboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalLaboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalLaboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalPhysiologically, 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 β<sub>2</sub>-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 β<sub>1</sub>- and β<sub>3</sub>-antagonists (10 nM atenolol and 100 nM L-748,337, respectively), indicating a dependence on both β<sub>1</sub>- and β<sub>3</sub>-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 β<sub>1</sub>- and β<sub>3</sub>-adrenoceptors, revealing a new mechanism by which adrenergic stimulation may influence cancer cell metabolism.https://www.mdpi.com/1422-0067/24/1/767lipid dropletsbreast cancerβ-adrenoceptorstumourigenesis |
| spellingShingle | Dany Silva Katarzyna Kacprzak Clara Quintas Jorge Gonçalves Paula Fresco Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways International Journal of Molecular Sciences lipid droplets breast cancer β-adrenoceptors tumourigenesis |
| title | Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways |
| title_full | Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways |
| title_fullStr | Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways |
| title_full_unstemmed | Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways |
| title_short | Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways |
| title_sort | activation of β adrenoceptors promotes lipid droplet accumulation in mcf 7 breast cancer cells via camp pka epac pathways |
| topic | lipid droplets breast cancer β-adrenoceptors tumourigenesis |
| url | https://www.mdpi.com/1422-0067/24/1/767 |
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