The MEK inhibitor PD98059 attenuates growth inhibition and death in gallic acid-treated Calu-6 lung cancer cells by preventing glutathione depletion.

Gallic acid (GA) is widely distributed in various plants and foods and has various biological effects. In this study, we investigated the effects of mitogen-activated protein kinase (MEK, JNK or p38) inhibitors on GA-induced Calu-6 lung cancer cell death in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. GA inhibited the growth of Calu-6 cells and induced apoptosis and/or necrosis accompanied by the loss of mitochondrial membrane potential (MMP; Δψm). ROS levels and the number of GSH-depleted cells were observed to be increased at 24 h. MEK inhibitor suppressed cell growth inhibition, death, MMP (Δψm) loss and GSH depletion induced by GA, but failed to suppress the increase in ROS levels. JNK inhibitor also somewhat suppressed cell growth inhibition, MMP (Δψm) loss and GSH depletion induced by GA, and limited the increase in ROS levels. By contrast, p38 inhibitor mildly enhanced GA-induced cell growth inhibition, MMP (Δψm) loss and the increase in ROS levels. In conclusion, MEK inhibitor suppressed GA-induced cell growth inhibition and death in Calu-6 cells. This was related to the prevention of GSH depletion.