Atrián-Blasco Elena, Sáez Javier, Rodriguez-Yoldi Maria Jesús, Cerrada Elena
Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Consejo Superior de Investigaciones Científicas, Universidad de Zaragoza, 50009 Zaragoza, Spain.
Departamento de Farmacología y Fisiología, Medicina Legal y Forense, Unidad de Fisiología, Facultad de Veterinaria, Ciber de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto Agroalimentario de Aragón (IA2), 50013 Zaragoza, Spain.
Biomedicines. 2024 Aug 5;12(8):1763. 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.
本研究调查了新型金（I）和铜（I）/锌（II）异核配合物对结肠癌的活性。对合成的异核金（I）-铜（I）和金（I）-锌（II）配合物进行了表征，并使用人结肠癌细胞系（Caco-2）评估了它们的抗癌活性。这些配合物表现出强大的细胞毒性，IC值处于低微摩尔范围内，并能有效诱导癌细胞凋亡。就配合物[Cu{Au(Spy)(PTA)}]PF（）而言，其细胞毒性比其单核前体高×10倍，同时对分化的健康细胞显示出低细胞毒性。机理研究表明，该配合物抑制硫氧还蛋白还原酶的活性，硫氧还蛋白还原酶是参与氧化还原调节的关键酶，除了导致DNA三级结构改变外，还会导致活性氧（ROS）水平升高和氧化应激。此外，这些配合物对牛血清白蛋白（BSA）表现出很强的结合亲和力，表明其具有有效药物递送和生物利用度的潜力。总的来说，这些发现突出了所研究的异核金（I）-铜（I）和金（I）-锌（II）配合物作为有前景的抗癌药物的潜力，特别是对结肠癌，通过它们破坏氧化还原稳态和诱导氧化应激介导的细胞死亡的能力。
