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.