In the present study, we investigated the pathway of apoptosis by water extract of Sophora tonkinensis Radix (SDG) in A549 human lung carcinoma cells. It was found that SDG could inhibit the cell viability and induce the apoptotic cell death of A549 cells in a dose-dependent manner as measured by hemocytometer counts, DAPI staining and flow cytometry analysis. Apoptosis of A549 cells by SDG treatment was associated with a down-regulation of anti-apoptotic Bcl-2 and Bcl-XL and inhibitor of apoptosis proteins (IAPs) expression. SDG treatment induced the proteolytic activation of caspase-3 and caspase-9, and a concomitant degradation and/or down-regulation of poly (ADP-ribose) polymerase (PARP) and phospholipase (PLC)-Ճ1 protein. Additionally, DNA fragmentation by SDG treatment was connected with the activation of inhibitor of caspase-activated DNase/DNA fragmentation factor 45 (ICAD/DFF45) protein expression. Taken together, these results indicated that the inhibitory effect of SDG in A549 cells was associated with the induction of apoptotic cell death through regulation of several major growth regulatory gene products such as Bcl-2 family expression and caspase protease activity, and SDG may have therapeutic potential in human lung cancer treatment. (Cancer Prev Res 12, 58-67, 2007)

Keywords: Sophora tonkinensis, A549 cells, Apoptosis, Bcl-2, Caspase