Objectives : This study was designed to elucidate the synergistic cytotoxic mechanisms of the co-treatment of Gagamjengac-tang (GGJAT) and As₂O₃ in human lung cancer cell line, H-157. Methods : The combination of GGJAT and As₂O₃ synergistically augmented the cytotoxicity of GGJAT and As₂O₃ in H157 cells. The cytotoxicity by the combination of these two drugs was revealed as apoptosis which was characterized by chromatin condensation and fragmentation in DAPI staining. Results : Antioxidant NAC completely blocked the apoptotic death of H-157 cells by GGJAT and As₂O₃. The apoptotic cytotoxicity of GGJAT and As₂O₃ was accompanied by the induction of DR4 and DR5 in RT-PCR. In addition, antioxidant enzymes such as SOD1, GSH synthetase and GSH reductase were also increased in H-157 cells treated with GGJAT and As₂O₃. However, of note, p53, Fas, FasL and TRAIL were not detected in H-157 cells treated with GGJAT and As₂O₃ by RT-PCR. Conclusions : These results suggest that the synergistic cytotoxicity of the co-treatment of H-457 cells treated with GGJAT and As₂O₃ may cause induction of death receptors DR4 and DR5 as well as reactive oxygen species.
