MAPK inhibitors augment gallic acid-induced A549 lung cancer cell death through the enhancement of glutathione depletion.

Gallic acid (GA) is involved in various biological processes such as cell growth inhibition and apoptosis through changes in reactive oxygen species (ROS). In the present study, we investigated the effects of MAPK (MEK, JNK or p38) inhibitors on cell death in GA-induced A549 lung cancer cells in relation to ROS and glutathione (GSH). Treatment with 100 µM GA inhibited the growth of A549 cells and induced apoptosis and/or necrosis, which was accompanied by the loss of mitochondrial membrane potential (MMP; ∆Ψ(m)). GA increased ROS levels as well as GSH depletion in A549 cells at 24 h. MEK inhibitor seemed to enhance cell growth inhibition by GA. This inhibitor also increased cell death, MMP (∆Ψ(m)) loss and GSH depletion in GA-treated A549 cells. Both JNK and p38 inhibitors intensified growth inhibition, cell death, MMP (∆Ψ(m)) loss and GSH depletion by GA. However, none of the MAPK inhibitors significantly altered ROS levels in GA-treated A549 cells. In conclusion, MAPK inhibitors enhanced growth inhibition and death in GA-treated A549 cells, which were correlated with GSH depletion rather than ROS levels.