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Mixed copper(ii)-phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response

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MORÁŇ Lukáš PIVETTA Tiziana MASURI Sebastiano VAŠÍČKOVÁ Kateřina WALTER Franziska PREHN Jochen ELKALAF Moustafa TRNKA Jan HAVEL Josef VAŇHARA Petr

Rok publikování 2019
Druh Článek v odborném periodiku
Časopis / Zdroj Metallomics
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www http://dx.doi.org/10.1039/c9mt00055k
Doi http://dx.doi.org/10.1039/c9mt00055k
Klíčová slova ENDOPLASMIC-RETICULUM STRESS; LIGAND COPPER(II) COMPLEXES; DNA CLEAVAGE; TUMOR-CELLS; CISPLATIN; 1_10-PHENANTHROLINE; PHENANTHROLINE; APOPTOSIS; BINDING; CYTOTOXICITY
Popis 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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