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Int. J. Mol. Sci. 2013, 14(4), 6597-6613; doi:10.3390/ijms14046597

Mechanisms Involved in the Pro-Apoptotic Effect of Melatonin in Cancer Cells

1,2,* , 1,2
1,2, 1, 1,2, 1,2
1,2, 1
1 Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo, c/Julian Claveria 6, 33006 Oviedo, Spain 2 Oncology Institute of Asturias, University of Oviedo, 33006 Oviedo, Spain 3 Institute of Molecular Medicine, Faculty of Medicine, University of Lisboa, Professor Egas Moniz Avenue, 1649-028 Lisboa, Portugal
* Author to whom correspondence should be addressed.
Received: 5 March 2013 / Revised: 18 March 2013 / Accepted: 20 March 2013 / Published: 25 March 2013
(This article belongs to the Special Issue Advances in the Research of Melatonin)
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It is well established that melatonin exerts antitumoral effects in many cancer types, mostly decreasing cell proliferation at low concentrations. On the other hand, induction of apoptosis by melatonin has been described in the last few years in some particular cancer types. The cytotoxic effect occurs after its administration at high concentrations, and the molecular pathways involved have been only partially determined. Moreover, a synergistic effect has been found in several cancer types when it is administered in combination with chemotherapeutic agents. In the present review, we will summarize published work on the pro-apoptotic effect of melatonin in cancer cells and the reported mechanisms involved in such action. We will also construct a hypothesis on how different cell signaling pathways may relate each other on account for such effect.
Keywords: melatonin; cancer cells; apoptosis; ROS melatonin; cancer cells; apoptosis; ROS
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Rodriguez, C.; Martín, V.; Herrera, F.; García-Santos, G.; Rodriguez-Blanco, J.; Casado-Zapico, S.; Sánchez-Sánchez, A.M.; Suárez, S.; Puente-Moncada, N.; Anítua, M.J.; Antolín, I. Mechanisms Involved in the Pro-Apoptotic Effect of Melatonin in Cancer Cells. Int. J. Mol. Sci. 2013, 14, 6597-6613.

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