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

Metallomics Pub Date: 2019-07-18 DOI: 10.1039/C9MT00055K

Abstract

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.

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