Mixed copper(ii)-phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31348483
DOI
10.1039/c9mt00055k
Knihovny.cz E-resources
- MeSH
- Phenanthrolines chemistry pharmacology MeSH
- Coordination Complexes chemistry pharmacology MeSH
- Humans MeSH
- Copper chemistry pharmacology MeSH
- Cell Line, Tumor MeSH
- Ovarian Neoplasms drug therapy metabolism MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Unfolded Protein Response drug effects MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Phenanthrolines MeSH
- Coordination Complexes MeSH
- Copper MeSH
- Antineoplastic Agents MeSH
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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