JV-acetyl-L-cysteine (NAC) alters cell cycle progression in ovarian cancer cells of epithelial origin

Continuous exposure of the human, ovarian, cancer cell line 2008 to NAC revealed significant toxicity as measured by cell adherence and trypan blue exclusion assays (ICW=100 M). As a cysteine-containing molecule NAC itself has antioxidant activity and is also capable of upregulating cellular concentrations of glutathione (GSH) through the supply of L-cysteine. It is the purpose of our investigation to determine the mechanism of cytotoxicity of NAC in 2008 cells. No changes in the intracellular GSH content were observed up to 24 h following the start of NAC exposure; this suggests that NAC acts through a GSH-independent mechanism. Analysis of cell cycle profiles following 100 iM NAC using propidium iodide DNA staining showed an increased number of 2008 cells in S phase 12 h following the start of drug exposure. At 24 h postexpsoure an increased percentage of the population was present in G2 phase. These events preceded a loss of viability as indicated by trypan blue exclusion. Similar cell cycle changes were not observed with the antioxidant ascorbic acid at equivalent toxic concentrations, suggesting that the changes in cell cycle progression were specific to NAC and not a general response to antioxidants.