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Melatonin Enhances Cisplatin and Radiation Cytotoxicity in Head and Neck Squamous Cell Carcinoma by Stimulating Mitochondrial ROS Generation, Apoptosis, and Autophagy
Joint Authors
Rodríguez-Ferrer, José Manuel
Fernandez-Gil, Beatriz I.
Guerra-Librero, Ana
Shen, Ying-Qiang
Florido, Javier
Martínez-Ruiz, Laura
García-López, Sergio
Adan, Christian
Rodríguez-Santana, César
Quiñones-Hinojosa, Alfredo
Fernández-Martínez, José
López, Luis C.
Escames, Germaine
Abdel Moneim, Ahmed E.
Acuna-Castroviejo, Dario
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-02-28
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Head and neck cancer is the sixth leading cancer by incidence worldwide.
Unfortunately, drug resistance and relapse are the principal limitations of clinical oncology for many patients, and the failure of conventional treatments is an extremely demoralizing experience.
It is therefore crucial to find new therapeutic targets and drugs to enhance the cytotoxic effects of conventional treatments without potentiating or offsetting the adverse effects.
Melatonin has oncostatic effects, although the mechanisms involved and doses required remain unclear.
The purpose of this study is to determine the precise underlying mitochondrial mechanisms of melatonin, which increase the cytotoxicity of oncological treatments, and also to propose new melatonin treatments in order to alleviate and reverse radio- and chemoresistant processes.
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 0.1, 0.5, 1, and 1.5 mM melatonin combined with 8 Gy irradiation or 10 μM cisplatin.
Clonogenic and MTT assays, as well as autophagy and apoptosis, involving flow cytometry and western blot, were performed in order to determine the cytotoxic effects of the treatments.
Mitochondrial function was evaluated by measuring mitochondrial respiration, mtDNA content (RT-PCR), and mitochondrial mass (NAO).
ROS production, antioxidant enzyme activity, and GSH/GSSG levels were analyzed using a fluorometric method.
We show that high concentrations of melatonin potentiate the cytotoxic effects of radiotherapy and CDDP in HNSCC, which are associated with increased mitochondrial function in these cells.
In HNSCC, melatonin induces intracellular ROS, whose accumulation plays an upstream role in mitochondria-mediated apoptosis and autophagy.
Our findings indicate that melatonin, at high concentrations, combined with cisplatin and radiotherapy to improve its effectiveness, is a potential adjuvant agent.
American Psychological Association (APA)
Fernandez-Gil, Beatriz I.& Guerra-Librero, Ana& Shen, Ying-Qiang& Florido, Javier& Martínez-Ruiz, Laura& García-López, Sergio…[et al.]. 2019. Melatonin Enhances Cisplatin and Radiation Cytotoxicity in Head and Neck Squamous Cell Carcinoma by Stimulating Mitochondrial ROS Generation, Apoptosis, and Autophagy. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1205021
Modern Language Association (MLA)
Fernandez-Gil, Beatriz I.…[et al.]. Melatonin Enhances Cisplatin and Radiation Cytotoxicity in Head and Neck Squamous Cell Carcinoma by Stimulating Mitochondrial ROS Generation, Apoptosis, and Autophagy. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-12.
https://search.emarefa.net/detail/BIM-1205021
American Medical Association (AMA)
Fernandez-Gil, Beatriz I.& Guerra-Librero, Ana& Shen, Ying-Qiang& Florido, Javier& Martínez-Ruiz, Laura& García-López, Sergio…[et al.]. Melatonin Enhances Cisplatin and Radiation Cytotoxicity in Head and Neck Squamous Cell Carcinoma by Stimulating Mitochondrial ROS Generation, Apoptosis, and Autophagy. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1205021
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205021