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dc.contributor.authorGuerra Librero Rite, Ana 
dc.contributor.authorFernández Gil, Beatriz Irene
dc.contributor.authorFlorido Ruiz, Javier 
dc.contributor.authorMartínez Ruiz, Laura 
dc.contributor.authorRodríguez Santana, César 
dc.contributor.authorShen, Ying-Qiang
dc.contributor.authorLópez Rodríguez, Alba 
dc.contributor.authorRusanova Rusanova, Iryna 
dc.contributor.authorAcuña Castroviejo, Darío 
dc.contributor.authorHaro Muñoz, Tomás de 
dc.contributor.authorEscames Rosa, Germaine
dc.identifier.citationGuerra-Librero, A.; Fernandez-Gil, B.I.; Florido, J.; Martinez-Ruiz, L.; Rodríguez-Santana, C.; Shen, Y.-Q.; García-Verdugo, J.M.; López-Rodríguez, A.; Rusanova, I.; Quiñones-Hinojosa, A.; et al. Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function. Antioxidants 2021, 10, 603. []es_ES
dc.descriptionThis study was funded by grants from the Ministerio de Economia, Industria y Competitividad y por el Fondo de Desarrollo Regional FEDER, Spain nº SAF2013-49019, SAF2017-85903-P, and from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (P07- CTS- 03135, P10- CTS- 5784, and CTS- 101), Spain. J.F. and L.M. have FPU fellowships from the Ministerio de Educación Cultura y Deporte, Spain. C.R.S. was a schorlarship holder from the Plan Propio de Investigación of the University of Granada.es_ES
dc.descriptionWe wish to thank Michael O’Shea for proofreading the paper.es_ES
dc.description.abstractMetabolic reprogramming, which is characteristic of cancer cells that rapidly adapt to the hypoxic microenvironment and is crucial for tumor growth and metastasis, is recognized as one of the major mechanisms underlying therapeutic resistance. Mitochondria, which are directly involved in metabolic reprogramming, are used to design novel mitochondria-targeted anticancer agents. Despite being targeted by melatonin, the functional role of mitochondria in melatonin's oncostatic activity remains unclear. In this study, we aim to investigate the role of melatonin in mitochondrial metabolism and its functional consequences in head and neck cancer. We analyzed the effects of melatonin on head and neck squamous cell carcinoma (HNSCC) cell lines (Cal-27 and SCC-9), which were treated with 100, 500, and 1500 mu M of melatonin for 1, 3, and 5 days, and found a connection between a change of metabolism following melatonin treatment and its effects on mitochondria. Our results demonstrate that melatonin induces a shift to an aerobic mitochondrial metabolism that is associated with changes in mitochondrial morphology, function, fusion, and fission in HNSCC. We found that melatonin increases oxidative phosphorylation (OXPHOS) and inhibits glycolysis in HNSCC, resulting in increased ROS production, apoptosis, and mitophagy, and decreased cell proliferation. Our findings highlight new molecular pathways involved in melatonin's oncostatic activity, suggesting that it could act as an adjuvant agent in a potential therapy for cancer patients. We also found that high doses of melatonin, such as those used in this study for its cytotoxic impact on HNSCC cells, might lead to additional effects through melatonin receptors.es_ES
dc.description.sponsorshipMinisterio de Economia, Industria y Competitividad y por el Fondo de Desarrollo Regional FEDER, Spain SAF2013-49019 SAF2017-85903-Pes_ES
dc.description.sponsorshipJunta de Andalucia P07-CTS-03135 P10-CTS-5784 CTS-101es_ES
dc.description.sponsorshipMinisterio de Educacion Cultura y Deporte, Spaines_ES
dc.description.sponsorshipPlan Propio de Investigacion of the University of Granadaes_ES
dc.rightsAtribución 3.0 España*
dc.subjectHead and neck cancer cellses_ES
dc.subjectFree radicalses_ES
dc.titleMelatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Functiones_ES

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Atribución 3.0 España
Except where otherwise noted, this item's license is described as Atribución 3.0 España