Organoruthenium complexes with benzo-fused pyrithiones overcome platinum resistance in ovarian cancer cells

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

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.

• Language: English
• Keywords: ruthenium, pyrithione, resistance to chemotherapy, cancer, ovarian, thioredoxin
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 21 str.
• Numbering: Vol. 13, iss. 10, art. 2493
• PID: 20.500.12556/RUL-135447
• UDC: 546.96:547.8:618.11-006
• ISSN on article: 2072-6694
• DOI: 10.3390/cancers13102493
• COBISS.SI-ID: 64129539
• Publication date in RUL: 15.03.2022

Record is a part of a journal

• Title: Cancers
• Shortened title: Cancers
• Publisher: MDPI
• ISSN: 2072-6694
• COBISS.SI-ID: 517914137

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 20.05.2021

Secondary language

• Language: Slovenian
• Keywords: rutenij, organorutenijevi kompleksi, piritioni, rak jajčnikov