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Melatonin is an indoleamine compound produced in the pineal gland and also a plant\u2010derived product. Both\n                    <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n                    and melatonin have been shown to inhibit cancer cell growth in numerous studies, but they have never been combined altogether as an anticolon cancer treatment. In this study, we investigated whether the association between\n                    <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n                    and melatonin leads to an enhanced antiproliferative and pro\u2010apoptotic activities in colon cancer\n                    <jats:styled-content style=\"fixed-case\">SW<\/jats:styled-content>\n                    480 and\n                    <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>\n                    o\n                    <jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>\n                    o cells. We found that combined treatment with\n                    <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n                    and melatonin significantly enhanced inhibition of cell viability and migration, promoted changes in cell morphology and spreading, and increased induction of apoptosis, thereby potentiating the effects of\n                    <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n                    alone in colon cancer cells. Moreover, we found that the enhanced effects of\n                    <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n                    and melatonin combination are mediated through simultaneous modulation of cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    \/caspase,\n                    <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\n                    9\/\n                    <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\n                    \u20102, and p300\/\n                    <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\n                    \u2010\u03baB signaling pathways. Combined treatment with\n                    <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n                    and melatonin triggered the release of cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    from the mitochondrial intermembrane space into the cytosol, induced cleavage of caspase and\n                    <jats:styled-content style=\"fixed-case\">PARP<\/jats:styled-content>\n                    proteins, enhanced inhibition of\n                    <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\n                    9 and\n                    <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\n                    \u20102 expression, promoted p300 and\n                    <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\n                    \u2010\u03baB translocation from cell nuclei to cytoplasm, and abrogated\n                    <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\n                    \u2010\u03baB binding and p300 recruitment to\n                    <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\n                    \u20102 promoter in colon cancer cells. These results, therefore, demonstrated that melatonin potentiated the antiproliferative and pro\u2010apoptotic effects of\n                    <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n                    in colon cancer cells by modulating multiple signaling pathways and suggest that such a combinational treatment might potentially become an effective way in colon cancer therapy.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12035","type":"journal-article","created":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T12:27:34Z","timestamp":1355228854000},"page":"406-416","source":"Crossref","is-referenced-by-count":61,"title":["Expression of Concern: Melatonin potentiates the antiproliferative and pro\u2010apoptotic effects of ursolic acid in colon cancer cells by modulating multiple signaling pathways"],"prefix":"10.1111","volume":"54","author":[{"given":"Jingshu","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncology in South China Sun Yat\u2010Sen University Cancer Center Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Cancer Stem Cell Dalian Medical University Cancer Center Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangbing","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China Sun Yat\u2010Sen University Cancer Center Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendan","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Cancer Stem Cell Dalian Medical University Cancer Center Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Tian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China Sun Yat\u2010Sen University Cancer Center Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyi","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China Sun Yat\u2010Sen University Cancer Center Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingbo","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China Sun Yat\u2010Sen University Cancer Center Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Tong","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangsheng","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China Sun Yat\u2010Sen University Cancer Center Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlin","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China Sun Yat\u2010Sen University Cancer Center Guangzhou China"},{"name":"State Key Laboratory of Targeted Drug for Tumors of Guangdong Province Guangzhou Double Bioproduct Inc. 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