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@article{1550502, author = {Moráň, Lukáš and Pivetta, Tiziana and Masuri, Sebastiano and Vašíčková, Kateřina and Walter, Franziska and Prehn, Jochen and Elkalaf, Moustafa and Trnka, Jan and Havel, Josef and Vaňhara, Petr}, article_location = {Cambridge}, article_number = {9}, doi = {http://dx.doi.org/10.1039/c9mt00055k}, keywords = {ENDOPLASMIC-RETICULUM STRESS; LIGAND COPPER(II) COMPLEXES; DNA CLEAVAGE; TUMOR-CELLS; CISPLATIN; 1_10-PHENANTHROLINE; PHENANTHROLINE; APOPTOSIS; BINDING; CYTOTOXICITY}, language = {eng}, issn = {1756-5901}, journal = {Metallomics}, title = {Mixed copper(ii)-phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response}, url = {http://dx.doi.org/10.1039/c9mt00055k}, volume = {11}, year = {2019} }
TY - JOUR ID - 1550502 AU - Moráň, Lukáš - Pivetta, Tiziana - Masuri, Sebastiano - Vašíčková, Kateřina - Walter, Franziska - Prehn, Jochen - Elkalaf, Moustafa - Trnka, Jan - Havel, Josef - Vaňhara, Petr PY - 2019 TI - Mixed copper(ii)-phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response JF - Metallomics VL - 11 IS - 9 SP - 1481-1489 EP - 1481-1489 PB - ROYAL SOC CHEMISTRY SN - 17565901 KW - ENDOPLASMIC-RETICULUM STRESS KW - LIGAND COPPER(II) COMPLEXES KW - DNA CLEAVAGE KW - TUMOR-CELLS KW - CISPLATIN KW - 1_10-PHENANTHROLINE KW - PHENANTHROLINE KW - APOPTOSIS KW - BINDING KW - CYTOTOXICITY UR - http://dx.doi.org/10.1039/c9mt00055k L2 - http://dx.doi.org/10.1039/c9mt00055k N2 - There is an ongoing need for the development of new cancer therapeutics that combine high cytotoxic efficiency with low side effects, and also override resistance to the first-line chemotherapeutics. Copper(II)–phenanthroline 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)–phenanthroline 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)–phenanthroline complexes. ER -
MORÁŇ, Lukáš, Tiziana PIVETTA, Sebastiano MASURI, Kateřina VAŠÍČKOVÁ, Franziska WALTER, Jochen PREHN, Moustafa ELKALAF, Jan TRNKA, Josef HAVEL and Petr VAŇHARA. Mixed copper(ii)-phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response. \textit{Metallomics}. Cambridge: ROYAL SOC CHEMISTRY, 2019, vol.~11, No~9, p.~1481-1489. ISSN~1756-5901. Available from: https://dx.doi.org/10.1039/c9mt00055k.
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