Apoptotic DNA endonuclease (DNase-gamma) gene transfer induces cell death accompanying DNA fragmentation in human glioma cells.
OBJECTIVE
Both the genetic restoration of the apoptotic pathway and the introduction of proapoptotic molecules are now drawing attention. Concerning apoptosis of human glioma cells induced by human interferon-beta protein, we found that DNA endonuclease (DNase-gamma) acts as an executive molecule. The authors investigated whether gene transfer of this DNase-gamma exerts some therapeutic effects on human glioma cells.


METHODS
We transduced U251SP, U251MG, and T98G human glioma cells with DNase-gamma gene via multilamellar cationic liposomes, monitored the growth of those cells, and carefully observed the cell-death pattern.


RESULTS
DNase-gamma gene transfer resulted in an overexpression of DNase-gamma protein and induced DNA fragmentation in gene-transferred cells. The cytotoxic effect rose with multiple inoculations of the liposome, suggesting a relationship between its expression and the therapeutic effect.


CONCLUSIONS
These results demonstrate that DNase-gamma gene transfer can induce apoptosis in human glioma cells, indicating its potential to become a future gene therapy strategy.
Saito
Ryuta
R
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Mizuno
Masaaki
M
Kumabe
Toshihiro
T
Yoshimoto
Takashi
T
Tanuma
Sei-ichi
S
Yoshida
Jun
J
D017209:Apoptosis; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology*; D002455:Cell Division; D004273:DNA, Neoplasm / Q000032:analysis; D004706:Endodeoxyribonucleases / Q000235:genetics*; D018014:Gene Transfer Techniques; D005910:Glioma / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D008081:Liposomes; D010957:Plasmids; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D008081:Liposomes; D004706:Endodeoxyribonucleases; C105124:deoxyribonuclease gamma