RT Journal Article
T1 Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function
A1 Guerra-Librero, Ana
A1 Fernandez-Gil, Beatriz I.
A1 Florido, Javier
A1 Martinez-Ruiz, Laura
A1 Rodríguez-Santana, César
A1 Shen, Ying-Qiang
A1 García-Verdugo, José M.
A1 López-Rodríguez, Alba
A1 Rusanova, Iryna
A1 Quiñones-Hinojosa, Alfredo
A1 Acuña-Castroviejo, Darío
A1 Marruecos, Jordi
A1 De Haro, Tomás
A1 Escames, Germaine
K1 Melatonin
K1 Head and neck cancer cells
K1 Mitochondria
K1 OXPHOS
K1 Glycolysis
K1 Mitophagy
K1 Apoptosis
K1 Free radicals
K1 Melatonina
K1 Mitocondrias
K1 Glucólisis
K1 Mitofagia
K1 Radicales libres
K1 Neoplasias de cabeza y cuello
AB 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.
PB MDPI
YR 2021
FD 2021-04-14
LK http://hdl.handle.net/10668/3992
UL http://hdl.handle.net/10668/3992
LA en
NO Guerra-Librero A, Fernandez-Gil BI, Florido J, Martinez-Ruiz L, Rodríguez-Santana C, Shen YQ, et al. Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function. Antioxidants (Basel). 2021 Apr 14;10(4):603.
DS RISalud
RD Apr 9, 2025