{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:25:59Z","timestamp":1773660359007,"version":"3.50.1"},"reference-count":78,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2013,3,25]],"date-time":"2013-03-25T00:00:00Z","timestamp":1364169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms14046597","type":"journal-article","created":{"date-parts":[[2013,3,26]],"date-time":"2013-03-26T04:34:12Z","timestamp":1364272452000},"page":"6597-6613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Mechanisms Involved in the Pro-Apoptotic Effect of Melatonin in Cancer Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Carmen","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"},{"name":"Oncology Institute of Asturias, University of Oviedo, 33006 Oviedo, Spain"}]},{"given":"Vanesa","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"},{"name":"Oncology Institute of Asturias, University of Oviedo, 33006 Oviedo, Spain"}]},{"given":"Federico","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"},{"name":"Institute of Molecular Medicine, Faculty of Medicine, University of Lisboa,  Professor Egas Moniz Avenue, 1649-028 Lisboa, Portugal"}]},{"given":"Guillermo","family":"Garc\u00eda-Santos","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"},{"name":"Oncology Institute of Asturias, University of Oviedo, 33006 Oviedo, Spain"}]},{"given":"Jezabel","family":"Rodriguez-Blanco","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"}]},{"given":"Sara","family":"Casado-Zapico","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"},{"name":"Oncology Institute of Asturias, University of Oviedo, 33006 Oviedo, Spain"}]},{"given":"Ana","family":"S\u00e1nchez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"},{"name":"Oncology Institute of Asturias, University of Oviedo, 33006 Oviedo, Spain"}]},{"given":"Santos","family":"Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"}]},{"given":"Noelia","family":"Puente-Moncada","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"},{"name":"Oncology Institute of Asturias, University of Oviedo, 33006 Oviedo, Spain"}]},{"given":"Mar\u00eda","family":"An\u00edtua","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"}]},{"given":"Isaac","family":"Antol\u00edn","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo,  c\/Julian Claveria 6, 33006 Oviedo, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2013,3,25]]},"reference":[{"key":"ref_1","first-page":"6121","article-title":"Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture","volume":"48","author":"Hill","year":"1988","journal-title":"Cancer Res"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1096\/fasebj.10.8.8666165","article-title":"Neurohormone melatonin prevents cell damage: Effect on gene expression for antioxidant enzymes","volume":"10","author":"Antolin","year":"1996","journal-title":"FASEB J"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0006-8993(02)02551-9","article-title":"Protective effect of melatonin in a chronic experimental model of Parkinson\u2019s disease","volume":"943","author":"Mayo","year":"2002","journal-title":"Brain Res"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1200\/JCO.2002.11.004","article-title":"Melatonin: From basic research to cancer treatment clinics","volume":"20","author":"Vijayalaxmi","year":"2002","journal-title":"J. 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