Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function

Antioxidants

Laura Martinez-Ruiz¹  César Rodríguez-Santana¹  Ying-Qiang Shen¹  BeatrizI. Fernandez-Gil¹  Iryna Rusanova¹  Darío Acuña-Castroviejo¹  Germaine Escames¹  Ana Guerra-Librero¹  Javier Florido¹  Alba López-Rodríguez¹  JoséM. García-Verdugo²  Alfredo Quiñones-Hinojosa³  Jordi Marruecos⁴  Tomás De Haro⁵ 

[1] Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain;Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, 46980 Valencia, Spain;Department of Neurologic Surgery, Mayo Clinic, Jacksonville 32224, FL, USA;Institut Català d’Oncologia (ICO), Hospital Universitari Dr. Josep Trueta, 17007 Girona, Spain;UGC de Laboratorios Clínicos, Hospital Universitario San Cecilio, 18016 Granada, Spain;

关键词: melatonin;    head and neck cancer cells;    mitochondria;    OXPHOS;    glycolysis;    mitophagy;   

DOI  :  10.3390/antiox10040603

来源: DOAJ

【 摘 要 】

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 µM 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.

【 授权许可】

Unknown