Melatonin modulates proliferation of pancreatic stellate cells through caspase-3 activation and changes in cyclin A and D expression
| Autor: | Matias Estaras, Jose M. Mateos, Gerardo Blanco, Ginés M. Salido, Fernando J. Peña, Daniel Vara, Antonio González, V. Roncero, Diego Lopez, Miguel Fernandez-Bermejo, Jose A. Tapia |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
endocrine system Physiology Cell Survival Cyclin D Cyclin A 030209 endocrinology & metabolism Caspase 3 Biochemistry Melatonin 03 medical and health sciences 0302 clinical medicine medicine Animals Viability assay Rats Wistar Cells Cultured Cyclin Cell Proliferation biology Chemistry Pancreatic Stellate Cells General Medicine Cell cycle Rats 030104 developmental biology Hepatic stellate cell Cancer research biology.protein hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Journal of physiology and biochemistry. 76(2) |
| ISSN: | 1877-8755 |
| Popis: | In this study, the effects of melatonin (1 μM–1 mM) on pancreatic stellate cells (PSC) have been examined. Cell viability and proliferation, caspase-3 activation, and the expression of cyclin A and cyclin D were analyzed. Our results show that melatonin decreased PSC viability in a time- and concentration-dependent manner. This effect was not inhibited by treatment of cells with MT1, MT2, calmodulin, or ROR-alpha inhibitors prior to melatonin addition. Activation of caspase-3 in response to melatonin was detected. The expression of cyclin A and cyclin D was decreased in cells treated with melatonin. Finally, changes in BrdU incorporation into the newly synthesized DNA of proliferating cells were also observed in the presence of melatonin. We conclude that melatonin, at pharmacological concentrations, modulates proliferation of PSC through activation of apoptosis and involving crucial regulators of the cell cycle. These actions might not require specific melatonin receptors. Our observations suggest that melatonin, at high doses, could potentially exert anti-fibrotic effects and, thus, could be taken into consideration as supportive treatment in the therapy of pancreatic diseases. |
| Databáze: | OpenAIRE |
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