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Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin

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.

Publication metadata

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


DOI: 10.1016/j.mce.2016.07.012

PubMed id: 27402602


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