Two novel chiral tetranucleate copper-based complexes: syntheses, crystal structures, inhibition of angiogenesis and the growth of human breast cancer<i>in vitro</i>and<i>in vivo</i>

Abstract

The single crystals of two novel chiral tetranucleate copper(II)-based complexes (TNCu-A and TNCu-B) containing <i>L</i>-methioninol-derived Schiff-bases were obtained. Their single structures were characterized by X-ray single crystal diffraction, infrared (IR) rays, elemental analysis, and liquid chromatography-mass spectrometry analysis. TNCu-A can effectively inhibit human umbilical vein endothelial cells (HUVECs) to form a tubular structure and it induces apoptosis of human triple-negative breast cancer MDA-MB-231 cells and HUVECs <i>in vitro</i> in a mitochondria dependent manner. Moreover, <i>in vivo</i> TNCu-A can remarkably inhibit the growth of triple-negative breast cancer from which MDA-MB-231 cells were xenografted into severely immunodeficient nude mice by inhibiting proliferation, inducing apoptosis of MDA-MB-231 cells by dramatically inhibiting the expression of the anti-apoptotic protein Bcl-2 and up-regulating the expressions of proapoptotic proteins caspase-9 and Bax, and simultaneously inhibiting tumor angiogenesis by decreasing the density of vascular endothelial cells and suppressing migration and even partially inducing apoptosis.