{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:54:16Z","timestamp":1790636056124,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,26]],"date-time":"2015-01-26T00:00:00Z","timestamp":1422230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Spanish Science Technology and Innovation Ministry","award":["SAF2010-19579"],"award-info":[{"award-number":["SAF2010-19579"]}]},{"name":"Spanish Science Technology and Innovation Ministry","award":["SAF2013-42012-P"],"award-info":[{"award-number":["SAF2013-42012-P"]}]},{"name":"Instituto de Investigaci\u00f3n Valdecilla","award":["APG\/12"],"award-info":[{"award-number":["APG\/12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Radiation and adjuvant endocrine therapy are nowadays considered a standard treatment option after surgery in breast cancer. Melatonin exerts oncostatic actions on human breast cancer cells. In the current study, we investigated the effects of a combination of radiotherapy and melatonin on human breast cancer cells. Melatonin (1\u00a0m<jats:sc>m<\/jats:sc>, 10\u00a0<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc> and 1\u00a0n<jats:sc>m<\/jats:sc>) significantly inhibited the proliferation of <jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content>\u20107 cells. Radiation alone inhibited the <jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content>\u20107 cell proliferation in a dose\u2010dependent manner. Pretreatment of breast cancer cells with melatonin 1\u00a0wk before radiation led to a significantly greater decrease of <jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content>\u20107 cell proliferation compared with radiation alone. Melatonin pretreatment before radiation also decreased G<jats:sub>2<\/jats:sub>\u2010M phase arrest compared with irradiation alone, with a higher percentage of cells in the G<jats:sub>0<\/jats:sub>\u2010G<jats:sub>1<\/jats:sub> phase and a lower percentage of cells in S phase. Radiation alone diminished <jats:styled-content style=\"fixed-case\">RAD<\/jats:styled-content>51 and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010protein kinase (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>cs) <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression, two main proteins involved in double\u2010strand <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> break repair. Treatment with melatonin for 7\u00a0days before radiation led to a significantly greater decrease in <jats:styled-content style=\"fixed-case\">RAD<\/jats:styled-content>51 and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2212<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>cs <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression compared with radiation alone. Our findings suggest that melatonin pretreatment before radiation sensitizes breast cancer cells to the ionizing effects of radiation by decreasing cell proliferation, inducing cell cycle arrest and downregulating proteins involved in double\u2010strand <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> break repair. These findings may have implications for designing clinical trials using melatonin and radiotherapy.<\/jats:p>","DOI":"10.1111\/jpi.12205","type":"journal-article","created":{"date-parts":[[2015,1,9]],"date-time":"2015-01-09T08:32:23Z","timestamp":1420792343000},"page":"189-197","source":"Crossref","is-referenced-by-count":66,"title":["Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double\u2010strand <scp>DNA<\/scp> break repair"],"prefix":"10.1111","volume":"58","author":[{"given":"Carolina","family":"Alonso\u2010Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology School of Medicine University of Cantabria and Instituto de Investigaci\u00f3n Valdecilla (IDIVAL) Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology School of Medicine University of Cantabria and Instituto de Investigaci\u00f3n Valdecilla (IDIVAL) Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Mart\u00ednez\u2010Campa","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology School of Medicine University of Cantabria and Instituto de Investigaci\u00f3n Valdecilla (IDIVAL) Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"G\u00f3mez\u2010Arozamena","sequence":"additional","affiliation":[{"name":"Department of Medical Physics School of Medicine University of Cantabria Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Cos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology School of Medicine University of Cantabria and Instituto de Investigaci\u00f3n Valdecilla (IDIVAL) Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,26]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"6121","article-title":"Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF\u20107) in culture","volume":"48","author":"Hill SM","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/frne.1999.0194"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026023394407"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.0.0100153"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cdp.2006.03.002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800908786733469"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2008.00559.x"},{"key":"e_1_2_7_9_1","first-page":"207","volume-title":"Advances in Cancer Drug Targets","author":"Cos S","year":"2012"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2004.00186.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21401"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canrad.2013.01.014"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canrad.2004.01.003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70333-4"},{"key":"e_1_2_7_15_1","first-page":"29","article-title":"Tamoxifen for women at high risk of breast cancer","volume":"6","author":"Nazarali SA","year":"2014","journal-title":"Breast Cancer (Dove Med Press)"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-13-0099"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr969"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.01.006"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710794183015"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(01)00059-0"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013301408464"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.1991.tb00007.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2003.00077.x"},{"key":"e_1_2_7_25_1","first-page":"4383","article-title":"Influence of melatonin on invasive and metastatic properties of MCF\u20107 human breast cancer cells","volume":"58","author":"Cos S","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1945"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2009.00742.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12150"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2012.01027.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0959-9673.2006.00474.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12007"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800910791190201"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605336"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.2174\/2212697X01999131127163625"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00940.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000227533"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950131204"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4275"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206679"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.19.1346"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.8.2684"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2007.02.006"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08467"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-407676-1.00001-9"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.77.061306.125255"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2005.08.007"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.16.5706-5715.2003"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R700039200"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.09312"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807990106"},{"key":"e_1_2_7_51_1","first-page":"219","article-title":"Elevated levels of Rad51 recombination protein in tumor cells","volume":"62","author":"Raderschall E","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2014.02.020"},{"key":"e_1_2_7_53_1","first-page":"6008","article-title":"Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA\u2010dependent protein kinase and poly(ADP\u2010ribose) polymerase\u20101","volume":"63","author":"Veuger SJ","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4165(98)00020-8"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-5002(03)00026-6"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.3109\/01480545.2012.737805"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401903"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(99)00262-3"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2008.02.006"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.01.089"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku503"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000461"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2004.02.006"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1600-079X.2003.00092.x"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1373.2000.22502.x"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjpi.12205","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjpi.12205","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T05:42:49Z","timestamp":1696225369000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.12205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,26]]},"references-count":64,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1111\/jpi.12205"],"URL":"https:\/\/doi.org\/10.1111\/jpi.12205","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,26]]}}}