Transient vs. prolonged histone hyperacetylation: effects on colon cancer cell growth, differentiation, and apoptosis
| Autor: | Brian F. Hinnebusch, James T. Wu, Sonia Y. Archer, Richard A. Hodin, Shufen Meng |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Programmed cell death Sodium-Potassium-Chloride Symporters Physiology medicine.medical_treatment Apoptosis Butyrate Biology Hydroxamic Acids Histones chemistry.chemical_compound Epidermal growth factor Cyclins Physiology (medical) Tumor Cells Cultured medicine Humans RNA Messenger Propidium iodide Insulin-Like Growth Factor I Epidermal Growth Factor Hepatology Growth factor Gastroenterology Acetylation Cell Differentiation Sodium butyrate Alkaline Phosphatase Blotting Northern Flow Cytometry Molecular biology Actins Butyrates Trichostatin A Biochemistry chemistry Carrier Proteins HT29 Cells Cell Division Fetal bovine serum medicine.drug |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 280:G482-G490 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.2001.280.3.g482 |
| Popis: | The role of histone hyperacetylation in regard to growth, differentiation, and apoptosis in colon cancer cells was assessed in an in vitro model system. HT-29 cells were grown in ±10% fetal bovine serum with either 5 mM sodium butyrate or 0.3 μM trichostatin A [single dose (T) or 3 doses 8 h apart (TR)] for 24 h. Serum-starved HT-29 cells were further treated with epidermal growth factor or insulin-like growth factor I for an additional 24 h. Apoptosis was quantified with propidium iodide and characterized by electron microscopy. Northern blot analyses were performed with cDNA probes specific for intestinal alkaline phosphatase, Na-K-2Cl cotransporter, the cell cycle inhibitor p21, and the actin control. Flow cytometric analysis revealed a time-dependent growth suppression along with early induction of p21 mRNA in the butyrate, T, and TR groups. Histone hyperacetylation, assessed by acid-urea-triton gel electrophoresis, was transient in the T group but persisted for up to 24 h in the butyrate and TR groups. Induction of apoptosis, growth factor unresponsiveness, and differentiation occurred in the butyrate- and TR-treated cells but not those treated with a single dose of trichostatin A. Thus transient hyperacetylation of histones is sufficient to induce p21 expression and produce cellular growth arrest, but prolonged histone hyperacetylation is required for induction of the programs of differentiation, apoptosis, and growth factor unresponsiveness. |
| Databáze: | OpenAIRE |
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