Increased expression of Transglutaminases 2 (TGase 2, TGase C) was observed in PC-14 human lung cancer cells in association with doxorubicin resistance and the reduction of the enzyme expression was correlated with the increasing cytotoxicity of the drug (Han and Park, 1999). Hydrogen peroxide was suggested to be a key mediator for doxorubicin-induced DNA fragmentation leading to apoptosis. A possible role of hydrogen peroxide as a putative mediator of TGase 2 expression in the doxorubicin sensitive PC-14 cells was examined. TGase 2 expression was increased in PC-14 cells treated with doxorubicin in a dose-dependent manner resulting in the concomitant increase of reactive oxygen species. The rise of TGase 2 expression by doxorubicin treatment was inhibited by N-acetylcysteine or glutathione treatment, while direct addition of hydrogen peroxide to PC-14 cells induced TGase 2 expression. These results suggest that generation of hydrogen peroxide induced by doxorubicin treatment is one of the key factors in an enhancement of TGase 2 expression in PC-14 cells.
Acetylcysteine/pharmacology ; Antineoplastic Agents/pharmacology* ; Doxorubicin/pharmacology* ; Enzyme Induction ; Gene Expression Regulation, Enzymologic ; Glutathione/pharmacology ; Human ; Hydrogen Peroxide/pharmacology ; Hydrogen Peroxide/metabolism* ; Lung Neoplasms/enzymology* ; Protein-Glutamine gamma-Glutamyltransferase/biosynthesis* ; Reactive Oxygen Species/metabolism ; Tumor Cells, Cultured/drug effects