Intracellular prooxidant activity of melatonin induces a survival pathway involving NF-kappaB activation.
We have shown that melatonin exerts a prooxidant activity in U937 cells, a tumor human promonocytic cell line. (1) Here we show that melatonin induces a strong canonical activation of NF-kappaB, inducing IkappaBalpha degradation and the consequential nuclear translocation of p50/p65 subunits. The timing of NF-kappaB activation overlaps with the timing of reactive oxygen species (ROS) production due to melatonin. Overexpression of dominant-negative IkappaB, which prevents a possible NF-kappaB activation, transformed melatonin in a proapoptotic molecule. These data indicate for the first time that melatonin can trigger NF-kappaB activation and might suggest a possible role for ROS induced by melatonin. Results indicate a possible involvement in the survival pathway of melatonin-generated ROS as secondary messengers.
Cristofanon
Silvia
S
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation Recherche sur le Cancer et les Maladies du Sang, Hôpital Kirchberg, Luxembourg. silvia.cristofanon@lbmcc.lu
Uguccioni
Francesco
F
Cerella
Claudia
C
Radogna
Flavia
F
Dicato
Mario
M
Ghibelli
Lina
L
Diederich
Marc
M
D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D020298:U937 Cells
D000975:Antioxidants; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009841:Oligonucleotides; D016877:Oxidants; D017382:Reactive Oxygen Species; D000072000:NF-KappaB Inhibitor alpha; D008550:Melatonin