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Lookup NU author(s): Professor Tiago OuteiroORCiD
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© 2016 Elsevier Ireland LtdMelatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antiproliferative, oncolytic and neuroprotective properties. Here, we present evidence that the N-acetyl side chain plays a key role in melatonin's antiproliferative effect in HT22 and sw-1353 cells, but it does so at the expense of antioxidant and neuroprotective properties. Removal of the N-acetyl group enhances the antioxidant and neuroprotective properties of the indole, but it can lead to toxic methamphetamine-like effects in several cell lines. Inhibition of NFkB mimicked melatonin's antiproliferative and antioxidant effects, but not neuroprotection. Our results strongly suggest that neuroprotective and antiproliferative effects of melatonin rely on different parts of the molecule and are likely mediated by different mechanisms. We also predict that melatonin metabolism by target cells could determine whether melatonin inhibits cell proliferation, prevents toxicity or induces cell death (e.g. apoptosis or autophagy). These observations could have important implications for the rational use of melatonin in personalized medicine.
Author(s): Letra-Vilela R, Sanchez-Sanchez AM, Rocha AM, Martin V, Branco-Santos J, Puente-Moncada N, Santa-Marta M, Outeiro TF, Antolin I, Rodriguez C, Herrera F
Publication type: Article
Publication status: Published
Journal: Molecular and Cellular Endocrinology
Year: 2016
Volume: 434
Pages: 238-249
Print publication date: 15/10/2016
Online publication date: 09/07/2016
Acceptance date: 07/07/2016
ISSN (print): 0303-7207
ISSN (electronic): 1872-8057
Publisher: Elsevier Ireland Ltd
URL: https://doi.org/10.1016/j.mce.2016.07.012
DOI: 10.1016/j.mce.2016.07.012
PubMed id: 27402602
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