Viral oncoapoptosis of human tumor cells.
Many cancer cells refractory to radiation treatment and chemotherapy proliferate because of loss of intrinsic programmed cell death (apoptosis) regulation. Consequently, the resolution of these cancers are many times outside the management capabilities of conventional therapeutics. We now report that replication-defective delta27 herpes simplex virus (rd delta27) triggers apoptosis in three representative transformed human cell lines. Susceptibility to virus-induced cell death is dependent on the abundance and distribution of modified p53 protein in the tumor cells indicating specific targeting of the treatment. Primary human and mouse fibroblast cells that produce modified p53 are resistant to rd delta27 killing but not to apoptosis induced by nonviral environmental factors. These results suggest that induction of apoptosis by nonreplicating virus is a feasible genetic therapy approach for killing human cancer cells. Our findings may have important implications in designing novel virus-based anticancer strategies in appropriate animal model systems.
Aubert
M
M
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Blaho
J A
JA
D000818:Animals; D017209:Apoptosis; D002461:Cell Line, Transformed / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000008:administration & dosage*; D005347:Fibroblasts / Q000473:pathology / Q000821:virology; D015316:Genetic Therapy / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008858:Microscopy, Phase-Contrast; D018139:Simplexvirus / Q000235:genetics*; D014162:Transfection / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014779:Virus Replication
D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53