Singly protonated dehydronorcantharidin silver coordination polymer induces apoptosis of lung cancer cells via reactive oxygen species-mediated mitochondrial pathway

•A novel silver complexe (Ag-SP-DNC) exhibited anticancer activity in vitro.•Ag-SP-DNC promoted the generation of reactive oxygen species in lung cancer cells.•Ag-SP-DNC induced apoptosis in lung cancer cells.•Ag-SP-DNC disrupted mitochondrial membrane potential, and activated caspase-3.•Ag-SP-DNC induced AIF and EndoG translocation to the nucleus.

Silver complexes have been shown to possess antimicrobial and anticancer properties. Ag-SP-DNC, a novel silver and singly protonated dehydronorcantharidin complex, was synthesized in our previous study. In this study, we offer evidence that Ag-SP-DNC elicits a reactive oxygen species (ROS)-mediated mitochondrial apoptosis in lung cancer cells. Ag-SP-DNC inhibited the growth of A549 cells by inducing G2/M phase cell cycle arrest and apoptosis. Ag-SP-DNC induced apoptosis was associated with the levels of intracellular ROS. The further study revealed that Ag-SP-DNC disrupted the mitochondrial membrane potential, induced the caspase-3 activation and led to the translocation of apoptosis inducing factor and endonucleaseG to the nucleus. These findings have important implications for the development of silver complexes for anticancer applications.

Graphical abstractAg-SP-DNC induces reactive oxygen species (ROS)-mediated mitochondrial apoptosis in lung cancer cells.Figure optionsDownload full-size imageDownload as PowerPoint slide