Arene Ruthenium(II) Complexes as Low-Toxicity Inhibitor against the Proliferation, Migration, and Invasion of MDA-MB-231 Cells through Binding and Stabilizing c-myc G-Quadruplex DNA
Qiong Wu, Kangdi Zheng, Siyan Liao, Yang Ding, Yangqiu Li, Wenjie Mei
Arene Ru(II) complexes have long been extensively studied as potential inhibitors against the proliferation of tumor cells, but their behavior against the migration and invasion of tumor cells needs further research. In this work, a series of arene Ru(II) complexes, (η6-C6H6)Ru(p-XPIP)Cl]Cl (X = H, 1; F, 2; Cl, 3; Br, 4; and I, 5), have been synthesized, and their inhibitory activity against the migration and invasion of MDA-MB-231 breast cancer cells have been investigated. It is found that all of these complexes exhibit excellent inhibitory activity (IC50) against the growth of MDA-MB-231 breast cancer cells, and the value of IC50 for 1, 2, 3, 4, and5 is about >300, 52.6, 11.4, 45.5, and 59.1 μM, respectively. Further studies by wound-healing assay, FITC-geltain assay, and flow cytometry assay showed that 3 can apparently suppress the migration and invasion of MDA-MB-231 cells via the joint action of S-phase arrest and apoptosis. Moreover, the binding behavior of these arene Ru(II) complexes with c-myc G-quadruplex DNA has also been studied, and the results showed that these complexes can bind and stabilize c-myc G-quadruplex DNA in groove binding mode. Also, the low toxicity of 3 was confirmed by its low inhibitory activity against the growth of normal MCF-10A breast cells in vitro and the development of zebrafish embryos in vivo. In other words, these results indicated that synthetic arene Ru(II) complexes can be developed as low-toxicity agents against the proliferation, migration, and invasion of breast cancer cells.
Circular dichroism, Pharmaceutical, Organic chemistry