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

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.

• Authors: Ryuta Saito, Masaaki Mizuno, Toshihiro Kumabe, Takashi Yoshimoto, Sei-ichi Tanuma, Jun Yoshida
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 63 Issue 1 Pg. 25-31 (May 2003) ISSN: 0167-594X [Print] United States
• PMID: 12814251 (Publication Type: Journal Article)

Chemical References

• DNA, Neoplasm
• Liposomes
• Endodeoxyribonucleases
• deoxyribonuclease gamma

Topics

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