The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells.
Nanomaterials and nanoparticles have received considerable attention recently because of their unique properties and diverse biotechnology and life sciences applications. Nanosilver products, which have well-known antimicrobial properties, have been used extensively in a range of medical settings. Despite the widespread use of nanosilver products, relatively few studies have been undertaken to determine the biological effects of nanosilver exposure. The purpose of this study was to evaluate the toxicity of nanosilver and to elucidate possible molecular mechanisms underlying the biological effects of nanosilver. Here, we show that nanosilver is cytotoxic, inducing apoptosis in NIH3T3 fibroblast cells. Treatment with nanosilver induced the release of cytochrome c into the cytosol and translocation of Bax to mitochondria, indicating that nanosilver-mediated apoptosis is mitochondria-dependent. Nanosilver-induced apoptosis was associated with the generation of reactive oxygen species (ROS) and JNK activation, and inhibition of either ROS or JNK attenuated nanosilver-induced apoptosis. In nanosilver-resistant HCT116 cells, up-regulation of the anti-apoptotic proteins, Bcl-2 appeared to be associated with a diminished apoptotic response. Taken together, our results provide the first evidence for a molecular mechanism of nanosilver cytotoxicity, showing that nanosilver acts through ROS and JNK to induce apoptosis via the mitochondrial pathway.
Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, Republic of China.
Yi-Hong
YH
Hsin
Chun-Feng
CF
Chen
Shing
S
Huang
Tung-Sheng
TS
Shih
Ping-Shan
PS
Lai
Pin Ju
PJ
Chueh
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D045325:HCT116 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis*; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D041681:NIH 3T3 Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018030:Silver Compounds / Q000633:toxicity*
D017382:Reactive Oxygen Species; D018030:Silver Compounds; D045304:Cytochromes c; D048670:MAP Kinase Kinase 4