Molecular analysis of the inhibitory effect of N-acetyl-L-cysteine on the proliferation and invasiveness of pancreatic cancer cells

Anticancer Drugs. 2013 Jun;24(5):504-18. doi: 10.1097/CAD.0b013e32836009d7.


Preliminary studies have suggested that the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) may be effective in inhibiting the growth of pancreatic cancer cells. In-depth cellular and molecular analyses were carried out to determine NAC's mode of action in inhibiting the growth of a well-characterized pancreatic cancer cell line (AsPC-1). Standardized assays were used to monitor cellular growth, apoptosis, levels of ROS, cellular senescence, migration, and invasiveness. Cell stiffness was measured using atomic force microscopy. Gene expression was monitored by quantitative PCR. NAC significantly inhibits the growth and metastatic potential of AsPC-1 cells by inducing cell-cycle arrest in G1 and subsequent cellular senescence and decreased invasiveness. These anticancer properties are associated with an unexpected increase in the intracellular concentrations of ROS. NAC does not decrease the susceptibility of AsPC-1 cells to the anticancer drugs gemcitabine, mitomycin C, and doxorubicin. NAC-induced changes in gene expression are consistent with the onset of mesenchymal-to-epithelial transition. In conclusion, our findings indicate that NAC induces an integrated series of responses in AsPC-1 cells that make it a highly promising candidate for development as a pancreatic cancer therapeutic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cellular Senescence / drug effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, myc
  • Humans
  • Mitomycin / pharmacology
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Reactive Oxygen Species / metabolism


  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Deoxycytidine
  • Mitomycin
  • Doxorubicin
  • Acetylcysteine
  • Gemcitabine