Gallic acid-induced lung cancer cell death is related to glutathione depletion as well as reactive oxygen species increase

Gallic acid (GA) widely distributed in plants and foods has its various biological effects. Here, we investigated the anti-cancer effects of GA on Calu-6 and A549 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH). GA dose-dependently decreased the growth of Calu-6 and A549 cells with an IC₅₀ of approximately 10-50μM and 100-200μM GA at 24h, respectively. GA also induced cell death in lung cancer cells, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨ_m). The percents of MMP (ΔΨ_m) loss and death cells were lower in A549 cells than Calu-6 cells. GA increased ROS levels including O2- in lung cancer cells at 24h and also GSH depleted cell numbers at this time. N-acetyl-cysteine (NAC; a well-known antioxidant) intensified growth inhibition and death in GA-treated lung cancer cells. NAC changed ROS levels and increased GSH depletion in these cells. Vitamin C significantly attenuated cell death, ROS levels and GSH depletion in GA-treated lung cancer cells. L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) slightly enhanced growth inhibition and death in GA-treated lung cancer cells and also mildly increased ROS levels and GSH depletion in these cells. In conclusion, GA inhibited the growth of lung cancer cells. GA-induced lung cancer cell death was related to GSH depletion as well as ROS level changes.