ABSTRACT
The single crystals of two novel copper(ii)-based complexes containing l-methioninol-derived Schiff bases were obtained and characterized. The nanoparticles of these complexes were prepared and their cellular uptake was measured in MDA-MB-231 cells and HUVECs. It was found that these complexes could remarkably induce apoptosis, inhibit proliferation, suppress migration and metastasis, and inhibit angiogenesis and the growth of triple-negative breast cancer derived from MDA-MB-231 cells in vitro. Meanwhile, these complexes exhibit anticancer and antiangiogenic functions by activating the important protein molecules VEGFR2, FAK, AKT and Erk1/2 or their phosphorylated molecules p-VEGFR2, p-FAK, p-AKT, and p-Erk1/2 in the VEGF/VEGFR2 signaling pathway, collapsing the mitochondrial membrane potential, and damaging the level of reactive oxygen species.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Coordination Complexes/pharmacology , Copper/pharmacology , Nanoparticles/chemistry , Protein Kinase Inhibitors/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Cell Survival/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Copper/chemistry , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Female , Humans , Models, Molecular , Molecular Structure , Particle Size , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Signal Transduction/drug effects , Surface Properties , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2/metabolismABSTRACT
Three novel single crystals of the metal-based complexes Cu-1, Cu-2, and Co-1 were obtained and characterized. Compared with Cu-2 and Co-1, Cu-1 showed remarkable activities of anti-cervical cancer, anti-cisplatin-resistant non-small cell lung cancer and anti-angiogenesis by downregulating the expressions of important proteins in the VEGF/VEGFR2 signaling pathway to inhibit angiogenesis and cancer cell proliferation, induce apoptosis, and suppress migration and metastasis. Moreover, Cu-1 dramatically inhibited the expression of the anti-apoptotic protein Bcl-2 and up-regulated the expressions of the proapoptotic proteins caspase-9 and Bax to induce the apoptosis of tumor cells, simultaneously decreasing the density of endothelial cells to inhibit tumor angiogenesis in cisplatin-resistant tumors.
