Mixed copper(ii)-phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
31348483
DOI
10.1039/c9mt00055k
Knihovny.cz E-zdroje
- MeSH
- fenantroliny chemie farmakologie MeSH
- komplexní sloučeniny chemie farmakologie MeSH
- lidé MeSH
- měď chemie farmakologie MeSH
- nádorové buněčné linie MeSH
- nádory vaječníků farmakoterapie metabolismus MeSH
- protinádorové látky chemie farmakologie MeSH
- signální dráha UPR účinky léků MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fenantroliny MeSH
- komplexní sloučeniny MeSH
- měď MeSH
- protinádorové látky 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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