Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function
| Autor: | Javier Florido, Ying Qiang Shen, Ana Guerra-Librero, Jordi Marruecos, Iryna Rusanova, Tomás de Haro, César Rodríguez-Santana, Darío Acuña-Castroviejo, Laura Martinez-Ruiz, José Manuel García-Verdugo, Alfredo Quiñones-Hinojosa, Alba López-Rodríguez, Germaine Escames, Beatriz Fernández-Gil |
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| Přispěvatelé: | [Guerra-Librero,A, Fernandez-Gil,BI, Florido,J, Martinez-Ruiz,L, Rodríguez-Santana,C, Shen,YQ, López-Rodríguez,A, Rusanova,I, Acuña-Castroviejo,D, Escames,G] Biomedical Research Center, Health Sciences Technology Park, University of Granada, Granada, Spain. [Guerra-Librero,A, Escames,G] CIBERFES, Ibs.Granada, San Cecilio University Hospital, Granada, Spain. [Florido,J, Escames,G] Department of Physiology, Faculty of Medicine, University of Granada, Granada, Spain. [García-Verdugo,JM] Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain. [Rusanova,I] Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada,Granada, Spain. [Quiñones-Hinojosa,A] Department of Neurologic Surgery, Mayo Clinic, Jacksonville, USA. [Marruecos,J] Institut Català d’Oncologia (ICO), Hospital Universitari Dr. Josep Trueta, Girona, Spain. [De Haro,T] UGC de Laboratorios Clínicos, Hospital Universitario San Cecilio, Granada, Spain., This study was funded by grants from the Ministerio de Economia, Industria y Competi tividad y por el Fondo de Desarrollo Regional FEDER, Spain n◦ 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 |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Phosphorylation::Oxidative Phosphorylation [Medical Subject Headings] Physiology Clinical Biochemistry melatonin Mitochondrion Biochemistry Melatonina Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] 0302 clinical medicine Anatomy::Cells::Cells Cultured::Cell Line [Medical Subject Headings] head and neck cancer cells Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance Neoplasm [Medical Subject Headings] Mitophagy Mitocondrias Chemistry apoptosis glycolysis OXPHOS mitochondria 030220 oncology & carcinogenesis hormones hormone substitutes and hormone antagonists medicine.drug Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Carbohydrate Metabolism::Glycolysis [Medical Subject Headings] Neoplasias de cabeza y cuello Diseases::Neoplasms::Neoplasms by Site::Head and Neck Neoplasms [Medical Subject Headings] Chemicals and Drugs::Inorganic Chemicals::Free Radicals::Reactive Oxygen Species [Medical Subject Headings] Mitofagia free radicals Oxidative phosphorylation Article Melatonin 03 medical and health sciences medicine Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation [Medical Subject Headings] Molecular Biology Radicales libres Cell growth Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::DNA-Binding Proteins::Receptors Cytoplasmic and Nuclear::Receptors Melatonin [Medical Subject Headings] Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings] lcsh:RM1-950 Anatomy::Cells::Cellular Structures::Subcellular Fractions::Mitochondria [Medical Subject Headings] Cell Biology medicine.disease Head and neck squamous-cell carcinoma Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings] Glucólisis 030104 developmental biology lcsh:Therapeutics. Pharmacology mitophagy Apoptosis Cancer cell Cancer research Chemicals and Drugs::Hormones Hormone Substitutes and Hormone Antagonists::Hormones::Melatonin [Medical Subject Headings] |
| Zdroj: | Antioxidants, Vol 10, Iss 603, p 603 (2021) Digibug: Repositorio Institucional de la Universidad de Granada Universidad de Granada (UGR) Digibug. Repositorio Institucional de la Universidad de Granada instname Antioxidants Volume 10 Issue 4 |
| Popis: | This 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. We wish to thank Michael O’Shea for proofreading the paper. Metabolic 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. Ministerio de Economia, Industria y Competitividad y por el Fondo de Desarrollo Regional FEDER, Spain SAF2013-49019 SAF2017-85903-P Junta de Andalucia P07-CTS-03135 P10-CTS-5784 CTS-101 Ministerio de Educacion Cultura y Deporte, Spain Plan Propio de Investigacion of the University of Granada |
| Databáze: | OpenAIRE |
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