Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., 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.
Inorg Chem. 2024 Oct 21;63(42):19769-19782. doi: 10.1021/acs.inorgchem.4c02988. Epub 2024 Oct 10.
Targeting inflammation and the molecules involved in the inflammatory process could be an effective cancer prevention and therapy strategy. Therefore, the use of anti-inflammatory strategies, such as NSAIDs and metal-based drugs, has become a promising approach for preventing and treating cancer by targeting multiple pathways involved in tumor progression. The present work describes new phosphane gold(I) complexes derived from nonsteroidal anti-inflammatory drugs as multitarget drugs against colon cancer. The antiproliferative effect of the most active complexes, [Au(L3)(JohnPhos)] (), [Au(L4)(CyJohnPhos)] () and [Au(L4)(JohnPhos)] () against colon cancer cells (Caco2-/TC7) seems to be mediated by the inhibition of the enzyme cyclooxygenase-1/2, modulation of reactive oxygen species levels by targeting thioredoxin reductase (TrxR) activity, and induction of apoptosis in cancer cells. Additionally, the three complexes exhibit high selectivity index values toward noncancerous cells. The research highlights the importance of maintaining cellular redox balance and the role of TrxR in cancer cell survival.
靶向炎症及炎症过程中的相关分子可能是一种有效的癌症预防和治疗策略。因此，使用抗炎策略，如 NSAIDs 和基于金属的药物，通过靶向肿瘤进展过程中的多个途径，成为预防和治疗癌症的一种有前途的方法。本工作描述了源自非甾体抗炎药物的新型膦金（I）配合物，作为针对结肠癌的多靶药物。最活跃的配合物Au(L3)(JohnPhos)、Au(L4)(CyJohnPhos)和Au(L4)(JohnPhos)对结肠癌细胞（Caco2-/TC7）的增殖抑制作用似乎是通过抑制环氧化酶-1/2 酶、通过靶向硫氧还蛋白还原酶 (TrxR) 活性调节活性氧水平以及诱导癌细胞凋亡来介导的。此外，这三种配合物对非癌细胞具有高选择性指数值。该研究强调了维持细胞氧化还原平衡的重要性以及 TrxR 在癌细胞存活中的作用。
