Effectiveness of trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer

Ann Thorac Surg. 2006 Mar;81(3):1034-42. doi: 10.1016/j.athoracsur.2005.06.059.


Background: A well-known histone deacetylase inhibitor, trichostatin A, was applied to non-small-cell lung cancer cells to determine whether inhibition of histone deacetylase leads to the production of proteins that either arrest tumor cell growth or lead to tumor cell death.

Methods: Trichostatin A (0.01 to 1.0 micromol/L) was applied to one normal lung fibroblast and four non-small-cell lung cancer lines, and its effect was determined by flow cytometry, annexin-V staining, immunoprecipitation, and Western blot analysis.

Results: Trichostatin A demonstrated tenfold greater growth inhibition in all four non-small-cell lung cancer lines compared with normal controls, with a concentration producing 50% inhibition ranging from 0.01 to 0.04 micromol/L for the tumor cell lines and 0.7 micromol/L for the normal lung fibroblast line. Trichostatin A treatment reduced the percentage of cells in S phase (10% to 23%) and increased G1 populations (10% to 40%) as determined by flow cytometry. Both annexin-V binding assay and upregulation of the protein, gelsolin (threefold to tenfold), demonstrated that the tumor cells were apoptotic, whereas normal cells were predominantly in cell cycle arrest. Trichostatin A increased histone H4 acetylation and expression of p21 twofold to 15-fold without significant effect on p16, p27, CDK2, and cyclin D1.

Conclusions: Collectively, these data suggest that inhibition of histone deacetylation may provide a valuable approach for lung cancer treatment. We evaluated trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclin D1 / metabolism
  • Enzyme Inhibitors / therapeutic use
  • Gelsolin / metabolism
  • Histone Deacetylase Inhibitors
  • Histones / metabolism
  • Humans
  • Hydroxamic Acids / therapeutic use*
  • Lung / drug effects
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Gelsolin
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Cyclin D1
  • trichostatin A