Mixed copper(ii)-phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response
Authors | |
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Year of publication | 2019 |
Type | Article in Periodical |
Magazine / Source | Metallomics |
MU Faculty or unit | |
Citation | 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. 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. |
web | http://dx.doi.org/10.1039/c9mt00055k |
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 |
Description | 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. |
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