Effectiveness of Trichostatin A as a Potential Candidate for Anticancer Therapy in Non–Small-Cell Lung Cancer

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 μmol/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 μmol/L for the tumor cell lines and 0.7 μmol/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.