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Open AccessArticle

Melatonin-Induced Cytoskeleton Reorganization Leads to Inhibition of Melanoma Cancer Cell Proliferation

Departamento de Morfología y Biología Celular, Redox Biology Group, Instituto Universitario Oncológico del Principado de Asturias (IUOPA), School of Medicine, University of Oviedo, C/Julian Claveria 6, 33006 Oviedo, Spain
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias (HUCA), Avda. Roma s/n, 33011 Oviedo, Spain
Institut de Genetique Moleculaire de Montpellier, University of Montpellier, CNRS, 34095 Montpellier, France
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 548;
Received: 18 December 2019 / Revised: 12 January 2020 / Accepted: 13 January 2020 / Published: 15 January 2020
Neuroindole melatonin, a hormone synthesized during the night mainly—but not exclusively—by the pineal gland of all vertebrates, functions as an adapting signal to the light-dark cycle. Its antioxidant, neuroprotective, anti-inflammatory, and antitumor properties are all well-known and widely reported. Melanoma is one of the most common carcinomas among developed countries and a type of tumor particularly difficult to fight back in medium/advanced stages. In contrast to other types of cancer, influence of melatonin on melanoma has been scarcely investigated. Thus, we have chosen the murine melanoma model B16-F10 cell line to study antiproliferative and antitumoral actions of melatonin. For this purpose, we combined both, cell culture and in vivo models. Melatonin reduced either, growth rate or migration of B16-F10 cells. Furthermore, melanin synthesis was altered by melatonin, promoting its synthesis. Melatonin also induced a G2/M cell cycle arrest and altered the cytoskeletal organization. To corroborate these results, we tested the effect of melatonin in the in vivo model of B16-F10 cell injection in the tail vein, which causes numerous lung metastases. Two different strategies of melatonin administration were used, namely, in drinking water, or daily intraperitoneal injection. However, contrary to what occurred in cell culture, no differences were observed between control and melatonin treated groups. Results obtained led us to conclude that melatonin exerts an antiproliferative and anti-migrating effect on this melanoma model by interfering with the cytoskeleton organization, but this pharmacological effect cannot be translated in vivo as the indole did not prevent metastasis in the murine model, suggesting that further insights into the effects of the indole in melanoma cells should be approached to understand this apparent paradox. View Full-Text
Keywords: melatonin; melanoma; B16-F10; cytoskeleton; metastasis melatonin; melanoma; B16-F10; cytoskeleton; metastasis
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Alvarez-Artime, A.; Cernuda-Cernuda, R.; Francisco-Artime-Naveda; Cepas, V.; Gonzalez-Menendez, P.; Fernadez-Vega, S.; Quiros-Gonzalez, I.; Sainz, R.M.; Mayo, J.C. Melatonin-Induced Cytoskeleton Reorganization Leads to Inhibition of Melanoma Cancer Cell Proliferation. Int. J. Mol. Sci. 2020, 21, 548.

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