title: N-acetylcysteine modulates the cytotoxic effects of Paclitaxel.
abstract: 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 mM NAC, 1.0 μM 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.
authors.affiliation: Medical Sciences Division, Northern Ontario School of Medicine, Thunder Bay, Canada.
authors.forename: Patricia Anne
authors.initials: PA
authors.lastname: Lyle
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Mitsopoulos
authors.forename: Zacharias E
authors.initials: ZE
authors.lastname: Suntres
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053455:Caspase 10 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D053455:Caspase 10; D053148:Caspase 3; C506438:CASP10 protein, human; D017239:Paclitaxel; D000111:Acetylcysteine