Disulfiram Chelated with Copper Promotes Apoptosis in Osteosarcoma via ROS/Mitochondria Pathway

Abstract

Disulfiram (DSF) chelated with copper has been confirmed to have a strong anti-tumor ability. In this study, we determined that DSF–Cu induced mitochondria-dependent apoptosis in osteosarcoma (OS), reflecting in DSF–Cu induces mitochondrial membrane potential decline, the production of reactive oxygen species (ROS), and inhibiting cells migration and invasion along with decreasing the concentration of intracellular glutathione (GSH) and facilitating the opening of mitochondrial permeability transition pore (PT) in osteosarcoma cells. These anti-tumor activities can be reversed by Cyclosporine A (CsA, PT inhibitors) and N-acetyl-L-cysteine (NAC, antioxidants). Our results suggested that DSF–Cu exerts its anti-tumor effects in OS via regulation of the ROS/Mitochondria pathway. Our findings provide the basis for DSF–Cu to treat osteosarcoma, even might develop as a potential therapy for other tumors.