Depsipeptide induces cell death in Hodgkin lymphoma-derived cell lines
| Autor: | Ingo Hartlapp, Andrea Kemkers, Ganna Weibert, Christian P. Pallasch, Daniel Re, Michael Hummel |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cancer Research Programmed cell death Blotting Western Apoptosis Cell Cycle Proteins Biology Romidepsin Downregulation and upregulation Depsipeptides medicine Tumor Cells Cultured Humans Epigenetics RNA Messenger Enzyme Inhibitors Cell Proliferation Oligonucleotide Array Sequence Analysis Depsipeptide Antibiotics Antineoplastic Gene Expression Regulation Leukemic Gene Expression Profiling Cell Cycle NF-kappa B Acetylation Hematology Molecular biology Hodgkin Disease Histone Deacetylase Inhibitors Oncology Cell culture Cancer research Histone deacetylase medicine.drug |
| Zdroj: | Leukemia research. 33(7) |
| ISSN: | 1873-5835 |
| Popis: | A variety of genetic and epigenetic abnormalities were characterized over the last years in Hodgkin and Reed-Sternberg (H-RS) cells of classic Hodgkin Lymphoma (cHL). It was speculated that simultaneous inhibition of multiple signalling pathways might be a promising strategy to target this tumor entity. In the present study we tested the effect of histone deacetylase (HDAC) inhibition using depsipeptide (also known as romidepsin, FK228, FR901228 or NSC-630176) in cHL cell lines in vitro. Molecular mechanisms of toxicity were analyzed using RNA expression analysis and functional assays. It is shown that depsipeptide is effective at submicromolar concentrations and acts mainly by apoptosis induction, upregulation of p21 and cell cycle inhibition in G2/M. Of special note, HDAC mediated toxicity in H-RS cells does not require RelA/p65 downregulation, which was previously shown to drive the malignant phenotype of H-RS cells. In summary, depsipeptide induced protein acetylation results in transcriptional changes of a large number of pathogenetically relevant genes and increased RelA/p65 binding activity in cHL cell lines. Our preclinical data suggest that HDAC inhibition using depsipeptide might be a promising approach for the treatment of cHL patients. |
| Databáze: | OpenAIRE |
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