title: In vitro cytotoxicity and induction of apoptosis by silica nanoparticles in human HepG2 hepatoma cells.
abstract: BACKGROUND
  Silica nanoparticles have been discovered to exert cytotoxicity and induce apoptosis in normal human cells. However, until now, few studies have investigated the cytotoxicity of silica nanoparticles in tumor cells.
  
  
  METHODS
  This study investigated the cytotoxicity of 7-50 nm silica nanoparticles in human HepG2 hepatoma cells, using normal human L-02 hepatocytes as a control. Cell nucleus morphology changes, cellular uptake, and expression of procaspase-9, p53, Bcl-2, and Bax, as well as the activity of caspase-3, and intracellular reactive oxygen species and glutathione levels in the silica nanoparticle-treated cells, were analyzed.
  
  
  RESULTS
  The antitumor activity of the silica nanoparticles was closely related to particle size, and the antiproliferation activity decreased in the order of 20 nm > 7 nm > 50 nm. The silica nanoparticles were also cytotoxic in a dose- and time-dependent manner. However, the silica nanoparticles showed only slight toxicity in the L-02 control cells, Moreover, in HepG2 cells, oxidative stress and apoptosis were induced after exposure to 7-20 nm silica nanoparticles. Expression of p53 and caspase-3 increased, and expression of Bcl-2 and procaspase-9 decreased in a dose-dependent manner, whereas the expression of Bax was not significantly changed.
  
  
  CONCLUSIONS
  A mitochondrial-dependent pathway triggered by oxidative stress mediated by reactive oxygen species may be involved in apoptosis induced by silica nanoparticles, and hence cytotoxicity in human HepG2 hepatic cancer cells.
authors.affiliation: Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Lu
authors.forename: Jiangchao
authors.initials: J
authors.lastname: Qian
authors.forename: Huanjun
authors.initials: H
authors.lastname: Zhou
authors.forename: Qi
authors.initials: Q
authors.lastname: Gan
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Jingxiong
authors.initials: J
authors.lastname: Lu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001693:Biological Transport, Active; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D050997:Nanomedicine; D053758:Nanoparticles / Q000633:toxicity / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D005978:Glutathione