title: Oncolytic activity of Sindbis virus in human oral squamous carcinoma cells.
abstract: BACKGROUND
  Sindbis virus (SIN) infection causes no or only mild symptoms (fever, rash, and arthralgia) in humans. However, SIN has a strong cytopathic effect (CPE) on various cancer cells. This study focuses on the oncolytic activity of SIN AR399 on oral cancer cells compared with reovirus, a well-known oncolytic virus that targets cancer cells.
  
  
  METHODS
  We analysed the cytotoxicity and growth of SIN in 13 oral squamous cell carcinoma (OSCC) cell lines (HSC-2, HSC-3, HSC-4, Ca9-22, H-1, Sa-3, KON, KOSC-2, OK-92, HO-1-N1, SCC-4, SAT, SKN-3) and normal human oral keratinocytes (NHOKs).
  
  
  RESULTS
  Sindbis virus infection induced CPE in 12 OSCC cell lines at a low multiplicity of infection (MOI) of 0.01, but not in the OSCC cell line, HSC-4 or NHOKs. Sindbis viral growth was not observed in NHOKs, whereas high SIN growth was observed in all OSCC cell lines, including HCS-4. The cytotoxicity and growth of SIN was the same as reovirus at an MOI of 20 in 12 OSCC cell lines. The CPE was shown, by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling assays, to be apoptotic cell death. Furthermore, quantitative RT-PCR of mRNA in HSC-3 and HSC-4 cells after SIN infection showed that activation of caspases, cytochrome c, and IkappaBalpha was associated with SIN-induced apoptosis.
  
  
  CONCLUSIONS
  As a replication-competent oncolytic virus, SIN may be a useful therapeutic modality for oral cancers.
authors.affiliation: Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Uzawa
authors.forename: A
authors.initials: A
authors.lastname: Kasamatsu
authors.forename: K
authors.initials: K
authors.lastname: Shinozuka
authors.forename: K
authors.initials: K
authors.lastname: Sakuma
authors.forename: M
authors.initials: M
authors.lastname: Yamatoji
authors.forename: M
authors.initials: M
authors.lastname: Shiiba
authors.forename: Y
authors.initials: Y
authors.lastname: Shino
authors.forename: H
authors.initials: H
authors.lastname: Shirasawa
authors.forename: H
authors.initials: H
authors.lastname: Tanzawa
mesh_terms: D018354:Alphavirus Infections; D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D020287:In Situ Nick-End Labeling; D009062:Mouth Neoplasms / Q000821:virology*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012845:Sindbis Virus / Q000502:physiology*; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D014764:Viral Proteins