In vitro and in silico studies of a Zn(II) complex as a potential therapeutic agent for breast cancer.

Breast cancer (BC) is one of the most life-threatening diseases of women's health worldwide. This work was conducted to assess the anti-BC potency of a new Zn(II)-based complex. The Zn(II) complex coordinated to dimethoxy-substituted bipyridine was synthesized and its molecular structure was elucidated as Zn(bpy) (bpy-Zn) by single-crystal X-ray diffraction, bpy represents 4,4'-dimethoxy-2,2'-bipyridine. The cytotoxicity results indicated that bpy-Zn, unlike cisplatin, acts potently and selectively on the human breast cancer cells (MCF-7) compared to normal murine embryo cells (NIH/3T3) by IC value of 4.6 ± 0.5 µm and selectivity index (SI) of 2.0 over 48 h. bpy-Zn and cisplatin showed anti-metastatic activity as evidenced by inhibition of the colony formation and cell migration. The flow cytometric assessment of MCF-7 cells supported that bpy-Zn and cisplatin exert their cytotoxic effect through the apoptotic pathway. Moreover, bpy-Zn could induce overproduction of intracellular reactive oxygen species (ROS) in MCF-7 cells. The apoptotic mechanism in bpy-Zn-treated MCF-7 cells is probably related to the regulation of apoptosis-relevant genes expression, including BAX and BCL2. Moreover, bpy-Zn is able to cleave pUC19 plasmid DNA through the hydrolytic reaction pathway. Finally, bpy-Zn's affinity towards antiapoptosis-related proteins, as a potential apoptosis inducer, as well as breast cancer-relevant proteins, as a potential anti-BC agent, was evaluated by in silico molecular docking studies. Altogether, the results of this work strongly evidenced that bpy-Zn can be the subject of experimental validation and clinical trials to introduce this complex as a promising BC therapeutic agent.