{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:44:55Z","timestamp":1790423095646,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,9,27]],"date-time":"2012-09-27T00:00:00Z","timestamp":1348704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2012,9,27]],"date-time":"2012-09-27T00:00:00Z","timestamp":1348704000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Spanish MICINN","award":["SAF2010-19579"],"award-info":[{"award-number":["SAF2010-19579"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Melatonin exerts oncostatic effects on breast cancer by interfering with the estrogen\u2010signaling pathways. Melatonin reduces estrogen biosynthesis in human breast cancer cells, surrounding fibroblasts and peritumoral endothelial cells by regulating cytokines that influence tumor microenvironment. This hormone also exerts antiangiogenic activity in tumoral tissue. In this work, our objective was to study the role of melatonin on the regulation of the vascular endothelial growth factor (VEGF) in breast cancer cells. To accomplish this, we cocultured human breast cancer cells (MCF\u20107) with human umbilical vein endothelial cells (HUVECs). VEGF added to the cultures stimulated the proliferation of HUVECs and melatonin (1\u00a0m\n                    <jats:sc>m<\/jats:sc>\n                    ) counteracted this effect. Melatonin reduced VEGF production and VEGF mRNA expression in MCF\u20107 cells. MCF\u20107 cells cocultured with HUVECs stimulated the endothelial cells proliferation and increased VEGF levels in the culture media. Melatonin counteracted both stimulatory effects on HUVECs proliferation and on VEGF protein levels in the coculture media. Conditioned media from MCF\u20107 cells increased HUVECs proliferation, and this effect was significantly counteracted by anti\u2010VEGF and 1\u00a0m\n                    <jats:sc>m<\/jats:sc>\n                    melatonin. All these findings suggest that melatonin may play a role in the paracrine interactions between malignant epithelial cells and proximal endothelial cells through a downregulatory action on VEGF expression in human breast cancer cells, which decrease the levels of VEGF around endothelial cells. Lower levels of VEGF could be important in reducing the number of estrogen\u2010producing cells proximal to malignant cells as well as decreasing tumoral angiogenesis.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12007","type":"journal-article","created":{"date-parts":[[2012,8,16]],"date-time":"2012-08-16T09:31:09Z","timestamp":1345109469000},"page":"373-380","source":"Crossref","is-referenced-by-count":91,"title":["Regulation of vascular endothelial growth factor by melatonin in human breast cancer cells"],"prefix":"10.1111","volume":"54","author":[{"given":"Virginia","family":"Alvarez\u2010Garc\u00eda","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology School of Medicine University of Cantabria 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 Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Alonso\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology School of Medicine University of Cantabria 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 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 Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1093"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986711797636072"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20075"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00665960"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(96)00401-7"},{"key":"e_1_2_7_7_1","first-page":"647","article-title":"Serum endothelial growth factor is often evaluated in disseminated cancer","volume":"3","author":"Salven P","year":"1997","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_8_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_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/frne.1999.0194"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026023394407"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.0.0100153"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cdp.2006.03.002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800908786733469"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2008.00559.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2004.00186.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21401"},{"key":"e_1_2_7_17_1","first-page":"2250","article-title":"Tumor necrosis factor \u03b1 and interleukin 11 secreted by malignant breast epitelial cells inhibit adipocyte differentiation by selectively down\u2010regulating CCAAT\/enhancer binding protein \u03b1 and peroxisome proliferator\u2010activated receptor \u03b3: mechasnism of desmoplastic reaction","volume":"61","author":"Meng L","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2007.05.027"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00911.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00940.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.11.1285"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052703199"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","unstructured":"CosS Gonz\u00e1lezA Alvarez\u2010Garc\u00edaVet\u00a0al.Melatonin and breast cancer: selective estrogen enzyme modulator actions. 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