dc.contributor | Instituto Universitario de Biomedicina (IBIOMED) | es_ES |
dc.contributor.author | Ordoñez, Raquel | |
dc.contributor.author | Fernández, Ana | |
dc.contributor.author | Prieto-Domínguez, Néstor | |
dc.contributor.author | Martínez, Laura | |
dc.contributor.author | García-Ruiz, Carmen | |
dc.contributor.author | Fernández-Checa, José C. | |
dc.contributor.author | Mauriz Gutiérrez, José Luis | |
dc.contributor.author | González Gallego, Javier | |
dc.contributor.other | Otros | es_ES |
dc.date | 2015-04-23 | |
dc.date.accessioned | 2016-12-19T16:32:54Z | |
dc.date.available | 2016-12-19T16:32:54Z | |
dc.date.issued | 2016-12-19 | |
dc.identifier.citation | Journal of Pineal Research, 2015, 59 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10612/5688 | |
dc.description | P. 178-189 | es_ES |
dc.description.abstract | Autophagy is a process that maintains homeostasis during stress, although it also
contributes to cell death under specific contexts. Ceramides have emerged as important
effectors in the regulation of autophagy, mediating the crosstalk with apoptosis. Melatonin
induces apoptosis of cancer cells; however, its role in autophagy and ceramide metabolism
has yet to be clearly elucidated. This study was aimed to evaluate the effect of melatonin
administration on autophagy and ceramide metabolism and its possible link with melatonininduced
apoptotic cell death in hepatocarcinoma (HCC) cells. Melatonin (2 mM) transiently
induced autophagy in HepG2 cells through JNK phosphorylation, characterized by increased
Beclin1 expression, p62 degradation and LC3II and LAMP2 colocalization, which translated
in decreased cell viability. Moreover, ATG5-silencing sensitized HepG2 cells to melatonin
induced-apoptosis, suggesting a dual role of autophagy in cell death. Melatonin enhanced
ceramide levels through both de novo synthesis and acid sphingomyelinase (ASMase)
stimulation. Serine palmitoyl transferase (SPT) inhibition with myriocin prevented melatonin
induced autophagy and ASMase inhibition with imipramine impaired autophagy flux.
However, ASMase inhibition partially protected HepG2 cells against melatonin while SPT
inhibition significantly enhanced cell death. Findings suggest a cross-talk between SPTmediated
ceramide generation and autophagy in protecting against melatonin, while specific
ASMase-induced ceramide production participates in melatonin-mediated cell death. Thus,
dual blocking of SPT and autophagy emerge as a potential strategy to potentiate the apoptotic
effects of melatonin in liver cancer cells | es_ES |
dc.language | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.subject | Medicina. Salud | es_ES |
dc.subject.other | Melatonin | es_ES |
dc.subject.other | Hepatocarcinoma | es_ES |
dc.subject.other | Autophagy | es_ES |
dc.subject.other | Ceramides | es_ES |
dc.subject.other | Palmitoyltransferase | es_ES |
dc.subject.other | Apoptosis | es_ES |
dc.title | Ceramide metabolism regulates autophagy and apoptotic-cell death induced by melatonin in liver cancer cells | es_ES |
dc.type | info:eu-repo/semantics/preprint | es_ES |