title: Inactivated Sendai virus induces apoptosis mediated by reactive oxygen species in murine melanoma cells.
abstract: OBJECTIVE
  This paper aims to investigate the apoptotic effect of inactivated Sendai virus (hemagglutinating virus of Japan-enveloped, HVJ-E) on murine melanoma cells (B16F10) and the possible mechanisms involved in the putative apoptotic reactions.
  
  
  METHODS
  B16F10 cells were treated with HVJ-E at various multiplicities of infection (MOI), and the reactive oxygen species (ROS), cell viability, and apoptosis were measured. Next, the roles of ROS in the regulation of Bcl-2/Bax and the activation of mitogen-activated protein kinase (MAPK) pathways in HVJ-E-treated B16F10 cells were analyzed. To further evaluate the cytotoxic effect of HVJ-E-generated ROS on B16F10 cells, HVJ-E was intratumorally injected, both with and without N-acetyl-L-cysteine (NAC), into melanoma tumors on BALB/c mice. Tumor volume was then monitored for 3 weeks, and the tumor proteins were separated for immunoblot assay.
  
  
  RESULTS
  Treatment of B16F10 cells with HVJ-E resulted in a dose-dependent inhibition of cell-viability and an induction of apoptosis. The latter effect was associated with the generation of ROS. Inhibition of ROS generation by NAC resulted in a significant reduction of HVJ-E-induced Erk1/2, JNK, and p38 MAPK activation. Additionally, ROS inhibition caused a decrease in the Bcl-2/Bax ratio as well as promoting activation of apoptosis both in vitro and in vivo.
  
  
  CONCLUSIONS
  These results suggest that HVJ-E possesses potential anticancer activity in B16F10 cells through ROS-mediated mitochondrial dysfunction involving the MAPK pathway.
authors.affiliation: College of Clinical Medicine of Yangzhou University, Yangzhou 225001, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China.
authors.forename: Ling Yu
authors.initials: LY
authors.lastname: Li
authors.affiliation: College of Clinical Medicine of Yangzhou University, Yangzhou 225001, Jiangsu, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D010253:Respirovirus Infections / Q000821:virology*; D029082:Sendai virus / Q000502:physiology*; D038301:Virus Inactivation
chemical_list: D017382:Reactive Oxygen Species; D019950:Mitogen-Activated Protein Kinase 1
keywords: Apoptosis; Inactivated Sendai virus (HVJ-E); MAPK; Reactive oxygen species