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Copper(ii)\u2013phenanthroline complexes are promising compounds that were shown previously to induce an immediate cytotoxic response over a panel of tumor cell lines in vitro. The molecular mechanism, however, remained unresolved. In this work we performed a thorough study of the copper(ii)\u2013phenanthroline complexes containing different imidazolidine-2-thione ligands in ovarian cancer cells, and revealed that these complexes induce endoplasmic reticulum (ER) stress and subsequently cell death mediated by the unfolded protein response. Alleviation of the ER-stress by tauroursodeoxycholic acid (TUDCA) attenuated the cytotoxic effects. In summary, we have identified a novel, ER-dependent, molecular mechanism mediating cytotoxic effects of copper(ii)\u2013phenanthroline complexes.<\/jats:p>","DOI":"10.1039\/c9mt00055k","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T10:44:18Z","timestamp":1563446658000},"page":"1481-1489","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Mixed copper(<scp>ii<\/scp>)\u2013phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response"],"prefix":"10.1093","volume":"11","author":[{"given":"Luk\u00e1\u0161","family":"Mor\u00e1\u0148","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-62500, Brno, Czech Republic; Fax: +420 54949 1320; Tel: +420 54949 7780"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9881-3584","authenticated-orcid":false,"given":"Tiziana","family":"Pivetta","sequence":"additional","affiliation":[{"name":"Department of Chemical and Geological Sciences, University of Cagliari, Monserrato, CA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8913-6251","authenticated-orcid":false,"given":"Sebastiano","family":"Masuri","sequence":"additional","affiliation":[{"name":"Department of Chemical and Geological Sciences, University of Cagliari, Monserrato, CA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2507-6437","authenticated-orcid":false,"given":"Kate\u0159ina","family":"Va\u0161\u00ed\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-62500, Brno, Czech Republic; Fax: +420 54949 1320; Tel: +420 54949 7780"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Walter","sequence":"additional","affiliation":[{"name":"Centre for Systems Medicine and Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Prehn","sequence":"additional","affiliation":[{"name":"Centre for Systems Medicine and Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moustafa","family":"Elkalaf","sequence":"additional","affiliation":[{"name":"Laboratory for Metabolism and Bioenergetics, Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic"},{"name":"Centre for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1786-7562","authenticated-orcid":false,"given":"Jan","family":"Trnka","sequence":"additional","affiliation":[{"name":"Laboratory for Metabolism and Bioenergetics, Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic"},{"name":"Centre for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6675-5671","authenticated-orcid":false,"given":"Josef","family":"Havel","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Masaryk University, Brno, Czech Republic"},{"name":"International Clinical Research Center, St. Anne\u2019s University Hospital, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7470-177X","authenticated-orcid":false,"given":"Petr","family":"Va\u0148hara","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-62500, Brno, Czech Republic; Fax: +420 54949 1320; Tel: +420 54949 7780"},{"name":"International Clinical Research Center, St. Anne\u2019s University Hospital, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,18]]},"reference":[{"key":"2021121516075400500_cit1","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3322\/caac.21456","article-title":"Ovarian cancer statistics, 2018","volume":"68","author":"Torre","year":"2018","journal-title":"Ca-Cancer J. 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