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-acetylcysteine (NAC) is a recognized antioxidant in culture studies and treatments for oxidative stress-related diseases, but in some cases, NAC is a pro-oxidant. To study the effect of NAC on cell proliferation in the presence or absence of ROS stress, we used the stable ROS generator gallic acid (GA) to treat CL1-0 lung cancer cell models with different antioxidant activities. Different antioxidant activities were achieved through the ectopic expression of different
single nucleotide polymorphisms. GA increased ROS levels in CL1-0/
cells and caused cell death but had no effect on CL1-0/
cells within 24 h. We found that 0.1 mM NAC eliminated GA-induced growth inhibition, but 0.5 mM NAC enhanced GA-induced CL1-0/
cell death. However, in the absence of GA, NAC exceeding 2 mM inhibited the growth of CL1-0/
cells more significantly than that of CL1-0/
cells. Without GA, NAC has an antioxidant effect. Under GA-induced ROS stress, NAC may have pro-oxidant effects. Each cell type has a unique range of ROS levels for survival. The levels of ROS in the cell determines the sensitivity of the cell to an antioxidant or pro-oxidant. Cells with different antioxidant capacities were used to show that the intracellular ROS level affects NAC function and provides valuable information for the adjuvant clinical application of NAC.