Gold nanoparticles trigger apoptosis and necrosis in lung cancer cells with low intracellular glutathione

Abstract

Previously 13 nm gold nanoparticles (GNPs) have been shown to display cytotoxicity to lung cancer cells when l-buthionine-sulfoximine (BSO) was used to decrease the expression of intracellular glutathione (GSH). In this study, we investigated how the GNPs induced cell death at the molecular level. Dual staining with fluorescent annexin V, and propidium iodide was used to discriminate apoptotic and necrotic cell death. We found that GNPs induced apoptosis and necrosis in lung cancer cells with low level of intracellular GSH. The disruption of F-actin and phosphorylation of H2AX induced by GNPs were both associated with apoptosis. The ER stress was caused, mitochondrial membrane potential was disrupted, intracellular calcium was elevated and intracellular caspase-3 was activated by GNPs in lung cancer cells with low intracellular GSH, while cell death could not be prevented by the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. The cells were further examined for caspase-independent death. After GNPs and BSO exposure, apoptosis inducing factor, endonuclease G, and glyceraldehyde-3-phosphate dehydrogenase translocated into the nuclei of apoptotic cells. Receptor-interacting protein 1 kinase inhibitor necrostatin-1 significantly decreased the PI positive cells that were induced by GNPs and BSO. Taken together, our results suggest that multiple modes of cell death are concurrently induced in GNPs-exposed lung cancer cells with low intracellular GSH, including apoptosis and necrosis. These results have important implications for GNPs in anticancer applications.