Zn-3, a Tris[3-(2-pyridyl)-pyrazolyl]borate zinc(II) complex, shows preferential antiproliferative effects on breast cancer rather than normal breast cells via oxidative stress

Abstract

The antiproliferative effects of Zn-3, a tris[3-(2-pyridyl)-pyrazolyl]borate zinc(II) complex, were reported previously in triple-negative breast cancer (TNBC) cells; however, its anticancer mechanisms were not assessed. This investigation evaluated the antiproliferative efficiency of Zn-3 in breast cancer and normal cells. Zn-3 demonstrates preferential antiproliferative effects on TNBC (HCC1937 and MDA-MB-468) and non-TNBC breast (MCF-7 and SKBR-3) cells rather than normal breast cells (H184B5F5/M10; M10). Zn-3 increased the quantity of subG1 cells, annexin V detection, pancaspase, and caspase 3, 8, and 9 activation, demonstrating extrinsic and intrinsic apoptosis-inducible effects on breast cancer cells. Furthermore, Zn-3 provoked oxidative stress (reactive oxygen species and mitochondrial superoxide), accompanied by the destruction of the mitochondrial membrane potential. Finally, Zn-3 causes oxidative DNA damage, evidenced by 8-hydroxy-2-deoxyguanosine detection. Utilizing N-acetylcysteine validated that Zn-3-generated oxidative stress acts on these antiproliferative mechanisms. Therefore, Zn-3 is a potential anti-breast-cancer agent displaying preferential antiproliferative function.