尽管化学疗法增加了癌症患者的预期寿命，但其有毒副作用仍然是一个重要挑战。最近，金属有机化合物如席夫碱铜配合物因其独特的抗癌活性成为下一代抗癌药物的有希望的候选物。本研究对双核铜(II)配合物-1和单核铜(II)配合物-2进行了进一步的抗癌机制分析。为此，进行了细胞存活率测试、细胞凋亡和细胞周期的流式细胞术分析、细胞迁移试验和基因表达分析。根据我们的结果，复合物-1在24/48小时的时间间隔内比复合物-2更具细胞毒性。我们的研究还表明，两种复合物在IC50浓度下均诱导细胞凋亡，并在G1-S检查点停滞细胞周期。然而，复合物-1在亚G0/G1期加速了细胞周期的停滞，而复合物-2没有。此外，基因表达分析显示，只有复合物-1诱导p53的表达。有趣的是，两种复合物均诱导了Bcl-2的过度表达。然而，它们都不影响MMP-13的表达。更有趣的是，这两种复合物通过招募非蛋白酶依赖的途径以不同方式抑制细胞迁移，包括变形和集体迁移。本研究证实了添加多个金属核和共配体可增加复合物的活性。同时，Cu含量的复合物似乎可以通过非蛋白酶依赖的途径阻止癌细胞的迁移，这可用于新的治疗目的。© 2023. 作者（们），在 Springer Science+Business Media, LLC 的独家许可下, Springer Nature 部分。

Although chemotherapy has increased the life expectancy of cancer patients, its toxic side effects remain a major challenge. Recently, organometallic compounds, such as Schiff base copper complexes, have become promising candidates for next-generation anticancer drugs owing to their unique anticancer activities. In this study, binuclear copper(II) complex-1 and mononuclear copper(II) complex-2 were examined to analyze their anticancer mechanisms further. For this purpose, a viability test, flow cytometry analysis of apoptosis and the cell cycle, migration assay, and gene expression analysis were performed. According to our results, complex-1 was more cytotoxic than complex-2 at 24/48-h intervals. Our findings also demonstrated that both complexes induced apoptosis at IC50 concentrations and arrested the cell cycle at the G1-S checkpoint. However, complex-1 accelerates cell cycle arrest at the sub-G0/G1 phase more than complex-2 does. Furthermore, gene expression analysis showed that only complex-1 induces the expression of p53. Interestingly, both complexes induced Bcl-2 overexpression. However, they did not affect MMP-13 expression. More interestingly, both complexes inhibited cell migration in different ways, including amoeboid and collective, by recruiting protease-independent pathways. This study confirmed that adding several metal cores and co-ligands increased the activity of the complex. It also appeared that Cu-containing complexes could prevent the migration of cancer cells through protease-independent pathways, which can be used for novel therapeutic purposes.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.