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Exposure to clastogenic agents such as heavy metals, ionizing radiation (IR), and chemotherapy drugs may cause chronic mutations in the genomic material, leading to a phenomenon named genomic instability. Evidence suggests that genomic instability is responsible for cancer incidence after exposure to carcinogenic agents, and increases the risk of secondary cancers following treatment with radiotherapy or chemotherapy. Melatonin as the main product of the pineal gland is a promising hormone for preventing cancer and improving cancer treatment. Melatonin can directly neutralize toxic free radicals more efficiently compared with other classical antioxidants. In addition, melatonin is able to regulate the reduction\/oxidation (redox) system in stress conditions. Through regulation of mitochondrial nction and inhibition of pro\u2010oxidant enzymes, melatonin suppresses chronic oxidative stress. Moreover, melatonin potently stimulates DNA damage responses that increase the tolerance of normal tissues to toxic effect of IR and may reduce the risk of genomic instability in patients who undergo radiotherapy. Through these mechanisms, melatonin attenuates several side effects of radiotherapy and chemotherapy. Interestingly, melatonin has shown some synergistic properties with IR and chemotherapy, which is distinct from classical antioxidants that are mainly used for the alleviation of adverse events of radiotherapy and chemotherapy. In this review, we describe the anticarcinogenic effects of melatonin and also its possible application in clinical oncology.<\/jats:p>","DOI":"10.1002\/jcp.27391","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T01:27:49Z","timestamp":1537579669000},"page":"5613-5627","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment"],"prefix":"10.1002","volume":"234","author":[{"given":"Bagher","family":"Farhood","sequence":"first","affiliation":[{"name":"Departments of Medical Physics and Radiology, Faculty of Paramedical Sciences Kashan University of Medical Sciences Kashan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasser Hashemi","family":"Goradel","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology School of Advanced Technologies in Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keywan","family":"Mortezaee","sequence":"additional","affiliation":[{"name":"Department of Anatomy School of Medicine, Kurdistan University of Medical Sciences Sanandaj Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Khanlarkhani","sequence":"additional","affiliation":[{"name":"Department of Anatomy School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Najafi","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Nuclear Medicine School of Paramedical Sciences, Kermanshah University of Medical Science Kermanshah Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8656-1444","authenticated-orcid":false,"given":"Amirhossein","family":"Sahebkar","sequence":"additional","affiliation":[{"name":"Neurogenic Inflammation Research Center Mashhad University of Medical Sciences Mashhad Iran"},{"name":"Biotechnology Research Center Pharmaceutical Technology Institute, Mashhad University of Medical Sciences Mashhad Iran"},{"name":"School of Pharmacy, Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,21]]},"reference":[{"key":"e_1_2_10_1_2_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2001.300201.x"},{"key":"e_1_2_10_1_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12205"},{"key":"e_1_2_10_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.10.015"},{"key":"e_1_2_10_1_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.5b04920"},{"key":"e_1_2_10_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.292"},{"key":"e_1_2_10_1_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230390257885"},{"key":"e_1_2_10_1_8_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v6.i4.230"},{"key":"e_1_2_10_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2004.05.005"},{"key":"e_1_2_10_1_10_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0306164"},{"key":"e_1_2_10_1_11_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2013.834890"},{"key":"e_1_2_10_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(01)00133-4"},{"key":"e_1_2_10_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2008.07.007"},{"issue":"18","key":"e_1_2_10_1_14_1","first-page":"4693","article-title":"Melatonin inhibition of cancer growth in vivo involves suppression of tumor fatty acid metabolism via melatonin receptor\u2010mediated signal transduction events","volume":"59","author":"Blask D. 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