Heteronuclear Complexes with Promising Anticancer Activity against Colon Cancer

Atrián-Blasco, Elena ; Sáez, Javier ; Rodriguez-Yoldi, Maria Jesús (Universidad de Zaragoza) ; Cerrada, Elena (Universidad de Zaragoza)

Resumen: This study investigates the activity of novel gold(I) and copper(I)/zinc(II) heteronuclear complexes against colon cancer. The synthesised heteronuclear Au(I)-Cu(I) and Au(I)-Zn(II) complexes were characterised and evaluated for their anticancer activity using human colon cancer cell lines (Caco-2). The complexes exhibited potent cytotoxicity, with IC50 values in the low micromolar range, and effectively induced apoptosis in cancer cells. In the case of complex [Cu{Au(Spy)(PTA)}2]PF6 (2), its cytotoxicity is ×10 higher than its mononuclear precursor, while showing low cytotoxicity towards differentiated healthy cells. Mechanistic studies revealed that complex 2 inhibits the activity of thioredoxin reductase, a key enzyme involved in redox regulation, leading to an increase in reactive oxygen species (ROS) levels and oxidative stress, in addition to an alteration in DNA’s tertiary structure. Furthermore, the complexes demonstrated a strong binding affinity to bovine serum albumin (BSA), suggesting the potential for effective drug delivery and bioavailability. Collectively, these findings highlight the potential of the investigated heteronuclear Au(I)-Cu(I) and Au(I)-Zn(II) complexes as promising anticancer agents, particularly against colon cancer, through their ability to disrupt redox homeostasis and induce oxidative stress-mediated cell death.

Idioma: Inglés

DOI: 10.3390/biomedicines12081763

Año: 2024

Publicado en: Biomedicines 12, 8 (2024), 1763 [20 pp.]
ISSN: 2227-9059

Financiación: info:eu-repo/grantAgreement/ES/CIBERObn/CB06-03-1012
Financiación: info:eu-repo/grantAgreement/ES/DGA/B16-23R
Financiación: info:eu-repo/grantAgreement/ES/DGA/E07-23R
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2019-104915RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-13686INB-I00
Financiación: info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/NEWPOWER-S1-1.1-E01116

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)
Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)