Jerneja Kladnik (Author), James P. C. Coverdale (Author), Jakob Kljun (Author), Hilke Burmeister (Author), Petra Lippman (Author), Francesca G. Ellis (Author), Alan M. Jones (Author), Ingo Ott (Author), Isolda Romero-Canelón (Author), Iztok Turel (Author)

Abstract

Drug resistance to existing anticancer agents is a growing clinical concern, with many first line treatments showing poor efficacy in treatment plans of some cancers. Resistance to platinum agents, such as cisplatin, is particularly prevalent in the treatment of ovarian cancer, one of the most common cancers amongst women in the developing world. Therefore, there is an urgent need to develop next generation of anticancer agents which can overcome resistance to existing therapies. We report a new series of organoruthenium(II) complexes bearing structurally modified pyrithione ligands with extended aromatic scaffold, which overcome platinum and adriamycin resistance in human ovarian cancer cells. The mechanism of action of such complexes appears to be unique from that of cisplatin, involving G$_1$ cell cycle arrest without generation of cellular ROS, as is typically associated with similar ruthenium complexes. The complexes inhibit the enzyme thioredoxin reductase (TrxR) in a model system and reduce cell motility towards wound healing. Importantly, this work highlights further development in our understanding of the multi-targeting mechanism of action exhibited by transition metal complexes.

Keywords

rutenij;organorutenijevi kompleksi;piritioni;rak jajčnikov;ruthenium;pyrithione;resistance to chemotherapy;cancer;ovarian;thioredoxin;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FKKT - Faculty of Chemistry and Chemical Technology
UDC: 546.96:547.8:618.11-006
COBISS: 64129539 Link will open in a new window
ISSN: 2072-6694
Views: 121
Downloads: 45
Average score: 0 (0 votes)
Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary language: Slovenian
Secondary keywords: rutenij;organorutenijevi kompleksi;piritioni;rak jajčnikov;
Type (COBISS): Article
Pages: str. 1-21
Volume: ǂVol. ǂ13
Issue: ǂiss. ǂ10
Chronology: May 2021
DOI: 10.3390/cancers13102493
ID: 14759897