title: Gallic acid-induced lung cancer cell death is related to glutathione depletion as well as reactive oxygen species increase.
abstract: 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 IC(50) of approximately 10-50 microM and 100-200 microM GA at 24h, respectively. GA also induced cell death in lung cancer cells, which was accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)). The percents of MMP (DeltaPsi(m)) loss and death cells were lower in A549 cells than Calu-6 cells. GA increased ROS levels including O(2)(-) 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.
authors.affiliation: Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Republic of Korea.
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: You
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity*; D001205:Ascorbic Acid / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000633:toxicity; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005707:Gallic Acid / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D005707:Gallic Acid; D005978:Glutathione; D001205:Ascorbic Acid; D000111:Acetylcysteine