Authors: Min Liu Xiaohu Gu Ke Zhang Yi Ding Xinbing Wei Xiumei Zhang Yunxue Zhao
Publish Date: 2013/07/30
Volume: 15, Issue: 8, Pages: 1745-
Abstract
Previously 13 nm gold nanoparticles GNPs have been shown to display cytotoxicity to lung cancer cells when lbuthioninesulfoximine 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 Factin 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 caspase3 was activated by GNPs in lung cancer cells with low intracellular GSH while cell death could not be prevented by the pancaspase inhibitor NbenzyloxycarbonylValAlaAspfluoromethylketone The cells were further examined for caspaseindependent death After GNPs and BSO exposure apoptosis inducing factor endonuclease G and glyceraldehyde3phosphate dehydrogenase translocated into the nuclei of apoptotic cells Receptorinteracting protein 1 kinase inhibitor necrostatin1 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 GNPsexposed lung cancer cells with low intracellular GSH including apoptosis and necrosis These results have important implications for GNPs in anticancer applicationsThe authors thank professor Paul V Murphy from National University of Ireland Galway for critically reviewing the manuscript This study was supported by the National Natural Science Foundation of China 81102468 to Y Zhao and the Natural Science Foundation of Shandong Province ZR2010HQ063 to Y Zhao
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