Potential of melatonin to reverse epigenetic aberrations in oral cancer

new findings


  • Emilio Gil-Martín Department of Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, 36310 Vigo, Spain. E-mail: egil@uvigo.es https://orcid.org/0000-0002-9435-0444
  • Eva Ramos Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain https://orcid.org/0000-0001-5791-0687
  • Francisco López-Muñoz Faculty of Health, Camilo José Cela University of Madrid (UCJC), 28692 Madrid, Spain; Neuropsychopharmacology Unit, Hospital 12 de Octubre Research Institute, 28041 Madrid, Spain https://orcid.org/0000-0002-5188-6038
  • Javier Egea Unidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa (IIS-IP), 28006 Madrid, Spain https://orcid.org/0000-0003-4704-3019
  • Alejandro Romero Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain. E-mail: manarome@ucm.es https://orcid.org/0000-0001-5483-4973




melatonin, oral cancer, epigenetic, gene expression, microRNAs, adjuvant therapy


It is now an accepted principle that epigenetic alterations cause cellular dyshomeostasis and functional changes, both of which are essential for the initiation and completion of the tumor cycle. Oral carcinogenesis is no exception in this regard, as most of the tumors in the different subsites of the oral cavity arise from the cross-reaction between (epi)genetic inheritance and the huge challenge of environmental stressors. Currently, the biochemical machinery is put at the service of the tumor program, halting the cell cycle, triggering uncontrolled proliferation, driving angiogenesis and resistance to apoptosis, until the archetypes of the tumor phenotype are reached. Melatonin has the ability to dynamically affect the epigenetic code. It has become accepted that melatonin can reverse (epi)genetic aberrations present in oral and other cancers, suggesting the possibility of enhancing the oncostatic capacity of standard multimodal treatments by incorporating this indolamine as an adjuvant. First steps in this direction confirm the potential of melatonin as a countermeasure to mitigate the detrimental side effects of conventional first-line radiochemotherapy. This single effect could produce synergies of extraordinary clinical importance, allowing doses to be increased and treatments not to be interrupted, ultimately improving patients’ quality of life and prognosis. Motivated by the urgency of improving the medical management of oral cancer, many authors advocate moving from in vitro and preclinical research, where the bulk of melatonin cancer research is concentrated, to systematic randomized clinical trials on large cohorts. Recognizing the challenge to improve the clinical management of cancer, our motivation is to encourage comprehensive and robust research to reveal the clinical potential of melatonin in oral cancer control. To improve the outcome and quality of life of patients with oral cancer, here we provide the latest evidence of the oncolytic activity that melatonin can achieve by manipulating epigenetic patterns in oronasopharyngeal tissue.



How to Cite

Gil-Martín, E., Ramos, E., López-Muñoz, F., Egea, J., & Romero, A. (2023). Potential of melatonin to reverse epigenetic aberrations in oral cancer: new findings. EXCLI Journal, 22, 1280–1310. https://doi.org/10.17179/excli2023-6624



Review articles