title: Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species.
abstract: BACKGROUND
  Zinc oxide nanoparticles (ZnO NPs) have received much attention for their implications in cancer therapy. It has been reported that ZnO NPs induce selective killing of cancer cells. However, the underlying molecular mechanisms behind the anticancer response of ZnO NPs remain unclear.
  
  
  RESULTS
  We investigated the cytotoxicity of ZnO NPs against three types of cancer cells (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human bronchial epithelial BEAS-2B) and two primary rat cells (astrocytes and hepatocytes). Results showed that ZnO NPs exert distinct effects on mammalian cell viability via killing of all three types of cancer cells while posing no impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA and protein levels of tumor suppressor gene p53 and apoptotic gene bax were upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NP-treated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3 enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative stress in HepG2 cells.
  
  
  CONCLUSIONS
  Overall, our data demonstrated that ZnO NPs selectively induce apoptosis in cancer cells, which is likely to be mediated by reactive oxygen species via p53 pathway, through which most of the anticancer drugs trigger apoptosis. This study provides preliminary guidance for the development of liver cancer therapy using ZnO NPs.
authors.affiliation: Department of Zoology, University of Lucknow, Lucknow, India.
authors.forename: Mohd Javed
authors.initials: MJ
authors.lastname: Akhtar
authors.forename: Maqusood
authors.initials: M
authors.lastname: Ahamed
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kumar
authors.forename: Ma Majeed
authors.initials: MM
authors.lastname: Khan
authors.forename: Javed
authors.initials: J
authors.lastname: Ahmad
authors.forename: Salman A
authors.initials: SA
authors.lastname: Alrokayan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D053938:DNA Fragmentation; D056945:Hep G2 Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015034:Zinc Oxide / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D015034:Zinc Oxide