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

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

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.

• Jezik: Angleški jezik
• Ključne besede: ruthenium, pyrithione, resistance to chemotherapy, cancer, ovarian, thioredoxin
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: 21 str.
• Številčenje: Vol. 13, iss. 10, art. 2493
• PID: 20.500.12556/RUL-135447
• UDK: 546.96:547.8:618.11-006
• ISSN pri članku: 2072-6694
• DOI: 10.3390/cancers13102493
• COBISS.SI-ID: 64129539
• Datum objave v RUL: 15.03.2022

Gradivo je del revije

• Naslov: Cancers
• Skrajšan naslov: Cancers
• Založnik: MDPI
• ISSN: 2072-6694
• COBISS.SI-ID: 517914137

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 20.05.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: rutenij, organorutenijevi kompleksi, piritioni, rak jajčnikov