Silver complexes are active constituents of the metal-based compounds; several studies suggest that silver complexes possess antimicrobial and anticancer properties. We have recently reported that Ag-SP-DNC, a novel silver and singly protonated dehydronorcantharidin complex, triggers oxidative stress-mediated apoptosis of lung cancer cells. In this study, we investigated the anticancer effects of Ag-SP-DNC in CT-26 murine colon carcinoma model. Ag-SP-DNC induced apoptosis of CT-26 cells, together with inhibition of cell proliferation; treatment of CT-26 tumor-bearing mice with Ag-SP-DNC delayed tumor growth. We also explored the mechanism of action of Ag-SP-DNC and found that Ag-SP-DNC treatment of CT-26 cells was associated with high levels of intracellular reactive oxygen species. The further experiments revealed that Ag-SP-DNC-treated cells underwent loss of mitochondrial membrane potential concomitant with intracellular calcium overload and caspase-3 activation. Taken together, our study demonstrates the potent anticancer effects of Ag-SP-DNC to colorectal cancer.

•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.Ag-SP-DNC induces reactive oxygen species (ROS)-mediated mitochondrial apoptosis in lung cancer cells.