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

MORÁŇ, Lukáš, Tiziana PIVETTA, Sebastiano MASURI, Kateřina VAŠÍČKOVÁ, Franziska WALTER, Jochen PREHN, Moustafa ELKALAF, Jan TRNKA, Josef HAVEL and Petr VAŇHARA. Mixed copper(ii)-phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response. Metallomics. Cambridge: ROYAL SOC CHEMISTRY, 2019, vol. 11, No 9, p. 1481-1489. ISSN 1756-5901. Available from: https://dx.doi.org/10.1039/c9mt00055k.

Basic information

• Original name: Mixed copper(ii)-phenanthroline complexes induce cell death of ovarian cancer cells by evoking the unfolded protein response
• Authors: MORÁŇ, Lukáš (203 Czech Republic, belonging to the institution), Tiziana PIVETTA (380 Italy), Sebastiano MASURI (380 Italy), Kateřina VAŠÍČKOVÁ (203 Czech Republic, belonging to the institution), Franziska WALTER (372 Ireland), Jochen PREHN (372 Ireland), Moustafa ELKALAF (203 Czech Republic), Jan TRNKA (203 Czech Republic), Josef HAVEL (203 Czech Republic, belonging to the institution) and Petr VAŇHARA (203 Czech Republic, guarantor, belonging to the institution).
• Edition: Metallomics, Cambridge, ROYAL SOC CHEMISTRY, 2019, 1756-5901.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10608 Biochemistry and molecular biology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 3.796
• RIV identification code: RIV/00216224:14110/19:00110493
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1039/c9mt00055k
• UT WoS: 000487053000003
• Keywords in English: ENDOPLASMIC-RETICULUM STRESS; LIGAND COPPER(II) COMPLEXES; DNA CLEAVAGE; TUMOR-CELLS; CISPLATIN; 1_10-PHENANTHROLINE; PHENANTHROLINE; APOPTOSIS; BINDING; CYTOTOXICITY
• Tags: 14110517, CF CELLIM, podil, rivok
• Tags: International impact, Reviewed

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.

Links

• EE2.3.20.0185, research and development project: Name: Centrum analýz a modelování tkání a orgánů
• LM2015062, research and development project: Name: Národní infrastruktura pro biologické a medicínské zobrazování

Investor: Ministry of Education, Youth and Sports of the CR

• MUNI/A/1565/2018, interní kód MU: Name: Zdroje pro tkáňové inženýrství 9 (Acronym: TissueEng 9)

Investor: Masaryk University, Category A