Heteronuclear Complexes with Promising Anticancer Activity against Colon Cancer

• Published in: Biomedicines Vol. 12; no. 8; p. 1763
• Main Authors: Atrián-Blasco, Elena, Sáez, Javier, Rodriguez-Yoldi, Maria Jesús, Cerrada, Elena
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.08.2024; MDPI
• Subjects: Antimitotic agents; Antineoplastic agents; Antineoplastic drugs; Antitumor activity; Apoptosis; Bioavailability; Bovine serum albumin; Cancer therapies; Cell death; Cell differentiation; Chemotherapy; Colon cancer; Colorectal cancer; Copper; Cytotoxicity; DNA structure; Drug delivery; Drug therapy; Gold; Health aspects; heteronuclear complexes; Homeostasis; Metals; Oxidative stress; Pharmaceutical research; Protein structure; Reactive oxygen species; ROS; Tertiary structure; Thioredoxin; thioredoxin reductase; Transition metal compounds; Tumor cell lines; Zinc; Spain; United States > US; gold; BSA; heteronuclear complexes; DNA; ROS; copper; zinc; thioredoxin reductase
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12081763

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 IC values in the low micromolar range, and effectively induced apoptosis in cancer cells. In the case of complex [Cu{Au(Spy)(PTA)} ]PF ( ), its cytotoxicity is ×10 higher than its mononuclear precursor, while showing low cytotoxicity towards differentiated healthy cells. Mechanistic studies revealed that complex 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.