Apoptotic DNA endonuclease (DNase-gamma) gene transfer induces cell death accompanying DNA fragmentation in human glioma cells

J Neurooncol. 2003 May;63(1):25-31. doi: 10.1023/a:1023771121240.

Abstract

Aims: 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.

MeSH terms

  • Apoptosis*
  • Blotting, Western
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / pathology*
  • Cell Division
  • DNA, Neoplasm / analysis
  • Endodeoxyribonucleases / genetics*
  • Gene Transfer Techniques
  • Glioma / enzymology*
  • Glioma / pathology*
  • Humans
  • Liposomes
  • Plasmids
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Liposomes
  • Endodeoxyribonucleases
  • deoxyribonuclease gamma