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

Abstract

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.

• Authors: Nishit K Mukhopadhyay, Ellen Weisberg, David Gilchrist, Raphael Bueno, David J Sugarbaker, Michael T Jaklitsch
• Journal: The Annals of thoracic surgery (Ann Thorac Surg) Vol. 81 Issue 3 Pg. 1034-42 (Mar 2006) ISSN: 1552-6259 [Electronic] Netherlands
• PMID: 16488717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Antineoplastic Agents (therapeutic use)
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, 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, pathology)