TY - JOUR
T1 - Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin
AU - Letra-Vilela, Ricardo
AU - Sánchez-Sánchez, Ana María
AU - Rocha, Ana Maia
AU - Martin, Vanesa
AU - Branco-Santos, Joana
AU - Puente-Moncada, Noelia
AU - Santa-Marta, Mariana
AU - Outeiro, Tiago Fleming
AU - Antolín, Isaac
AU - Rodriguez, Carmen
AU - Herrera, Federico
PY - 2016/10/15
Y1 - 2016/10/15
N2 - Melatonin (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.
AB - Melatonin (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.
KW - 5-Methoxy
KW - Autophagy
KW - Cell proliferation
KW - Melatonin
KW - N-acetyl
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=84978194791&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2016.07.012
DO - 10.1016/j.mce.2016.07.012
M3 - Article
AN - SCOPUS:84978194791
VL - 434
SP - 238
EP - 249
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
ER -