Oncolytic activity of Sindbis virus in human oral squamous carcinoma cells.
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.
Saito
K
K
Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Uzawa
K
K
Kasamatsu
A
A
Shinozuka
K
K
Sakuma
K
K
Yamatoji
M
M
Shiiba
M
M
Shino
Y
Y
Shirasawa
H
H
Tanzawa
H
H
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
D014764:Viral Proteins