Teixeira-Guedes Catarina, Brás Ana Rita, Teixeira Ricardo G, Valente Andreia, Preto Ana
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Institute of Science and Innovation for Bio-Sustainability (IB-S), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Pharmaceutics. 2022 Jun 17;14(6):1293. doi: 10.3390/pharmaceutics14061293.
Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in the treatment of CRC. This work aims to evaluate anti-CRC properties, as well as to identify the mechanisms of action of ruthenium complexes with the general formula [Ru(η-CHR)(PPh)(4,4'-R'-2,2'-bipyridine)][CFSO], where R = CH, CHO or CHOH and R' = H, CH, CHOH, or dibiotin ester. The complexes (Ru 1-7) displayed high bioactivity, as shown by low IC concentrations against CRC cells, namely, RKO and SW480. Four of the most promising ruthenium complexes (Ru 2, 5-7) were phenotypically characterized and were shown to inhibit cell viability by decreasing cell proliferation, inducing cell cycle arrest, and increasing apoptosis. These findings were in accordance with the inhibition of MEK/ERK and PI3K/AKT signaling pathways. Ruthenium complexes also led to a decrease in cellular clonogenic ability and cell migration, which was associated with the disruption of F-actin cytoskeleton integrity. Here, we demonstrated that ruthenium complexes, especially Ru7, have a high anticancer effect against CRC cells and are promising drugs to be used as a new therapeutical strategy for CRC treatment.
结直肠癌（CRC）是最常见的恶性肿瘤之一，也是全球癌症相关死亡的主要原因之一，因此迫切需要新的、更有效的治疗方法。在结直肠癌治疗中，钌配合物已成为传统铂类化合物有吸引力的替代品。本研究旨在评估通式为[Ru(η-CHR)(PPh)(4,4'-R'-2,2'-联吡啶)][CFSO]（其中R = CH、CHOH 或 CHO，R' = H、CH、CHOH 或二生物素酯）的钌配合物的抗结直肠癌特性，并确定其作用机制。这些配合物（Ru 1-7）表现出高生物活性，对结直肠癌细胞（即RKO和SW480）的低IC浓度表明了这一点。对四种最有前景的钌配合物（Ru 2、5-7）进行了表型特征分析，结果表明它们通过减少细胞增殖、诱导细胞周期停滞和增加细胞凋亡来抑制细胞活力。这些发现与MEK/ERK和PI3K/AKT信号通路的抑制一致。钌配合物还导致细胞克隆形成能力和细胞迁移减少，这与F-肌动蛋白细胞骨架完整性的破坏有关。在此，我们证明钌配合物，尤其是Ru7，对结直肠癌细胞具有高抗癌作用，有望作为结直肠癌治疗的新治疗策略的药物。
