N-Acetylcysteine Modulates the Cytotoxic Effects of Paclitaxel

Background: Paclitaxel is a microtubule-stabilizing drug known to cause mitotic G2/M arrest and apoptosis. It also increases the generation of reactive oxygen species (ROS) known to be involved in both apoptotic and necrotic cell death. Antioxidants, such as N-acetylcysteine (NAC), prevent the deleterious effects of ROS and modulate the regulation of apoptotic-linked cellular proteins. Methods: A549 human adenocarcinoma alveolar epithelial cells were treated with 5.0 m M NAC, 1.0 mu M paclitaxel, or co-incubated with both NAC and paclitaxel for a 24-hour incubation period. The effects of NAC in paclitaxel-induced cytotoxicity were evaluated by measuring cell viability, production of ROS, and apoptosis. Results: Challenge of cells with paclitaxel resulted in time/concentration-dependent decreases in cell viability and increases in intracellular levels of ROS, and apoptosis, all effects being abrogated by co-treatment with NAC. NAC reduced the paclitaxel-induced increase in activated caspase-10 levels, but potentiated that for caspase-3. Conclusions: NAC alters the cytotoxicity of paclitaxel in vitro by decreasing the levels of ROS, preventing apoptosis, and modulating apoptotic cellular proteins. Copyright (C) 2011 S. Karger AG, Basel