Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport.
apoptosis
head and neck cancer cells
melatonin
mitochondria
oxidative damage
reactive oxygen species
reverse electron transport
Journal
Journal of pineal research
ISSN: 1600-079X
Titre abrégé: J Pineal Res
Pays: England
ID NLM: 8504412
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
revised:
27
07
2022
received:
09
05
2022
accepted:
16
08
2022
pubmed:
21
8
2022
medline:
11
9
2022
entrez:
20
8
2022
Statut:
ppublish
Résumé
The oncostatic effects of melatonin correlate with increased reactive oxygen species (ROS) levels, but how melatonin induces this ROS generation is unknown. In the present study, we aimed to elucidate the two seemingly opposing actions of melatonin regarding its relationship with free radicals. We analyzed the effects of melatonin on head and neck squamous cell carcinoma cell lines (Cal-27 and SCC-9), which were treated with 0.5 or 1 mM melatonin. We further examined the potential effects of melatonin to induce ROS and apoptosis in Cal-27 xenograft mice. Here we report that melatonin mediates apoptosis in head and neck cancer by driving mitochondrial reverse electron transport (RET) to induce ROS production. Melatonin-induced changes in tumoral metabolism led to increased mitochondrial activity, which, in turn, induced ROS-dependent mitochondrial uncoupling. Interestingly, mitochondrial complex inhibitors, including rotenone, abolished the ROS elevation indicating that melatonin increased ROS generation via RET. Melatonin also increased membrane potential and CoQ
Identifiants
pubmed: 35986493
doi: 10.1111/jpi.12824
pmc: PMC9541246
doi:
Substances chimiques
Reactive Oxygen Species
0
Melatonin
JL5DK93RCL
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12824Subventions
Organisme : European Regional Development Fund (B-CTS-071-UGR18)
Organisme : Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (P18-RT-32222)
Organisme : Ministerio de Ciencia e Innovación/AEI: Agencia Estatal de Investigación/10.13039/501100011033/Financiado por la Unión Europea "NextGenerationEU"/PRTR (SAF2017-85903-P; PID2020-115112RB-I00)
Organisme : Ministerio de Educación, Cultura y Deporte (ayuda para contratos Predoctorales: FPU16/05304; FPU17/01549)
Organisme : Funding for open access charge: CBUA/Universidad de Granada
Informations de copyright
© 2022 The Authors. Journal of Pineal Research published by John Wiley & Sons Ltd.
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