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

Varování

Publikace nespadá pod Filozofickou fakultu, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.

Autoři	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.
Související projekty:	Centrum analýz a modelování tkání a orgánů National research infrastructure for biological and medical imaging Zdroje pro tkáňové inženýrství 9