Suberoylanilide hydroxamic acid (SAHA) at subtoxic concentrations increases the adhesivity of human leukemic cells to fibronectin
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19911379
DOI
10.1002/jcb.22397
Knihovny.cz E-resources
- MeSH
- Integrin beta1 metabolism MeSH
- Apoptosis drug effects MeSH
- Cell Adhesion drug effects MeSH
- Fibronectins metabolism MeSH
- Hydroxamic Acids pharmacology MeSH
- Leukemia metabolism MeSH
- Humans MeSH
- Lymphocytes drug effects metabolism MeSH
- Cell Line, Tumor MeSH
- Paxillin metabolism MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Antineoplastic Agents pharmacology MeSH
- Flow Cytometry MeSH
- Cell Separation MeSH
- Vorinostat MeSH
- Blotting, Western MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Integrin beta1 MeSH
- Fibronectins MeSH
- Hydroxamic Acids MeSH
- Paxillin MeSH
- Antineoplastic Agents MeSH
- Vorinostat MeSH
Suberoylanilide hydroxamic acid (SAHA) is an inhibitor of histone deacetylases (HDACs) which is being introduced into clinic for the treatment of hematological diseases. We studied the effect of this compound on six human hematopoietic cell lines (JURL-MK1, K562, CML-T1, Karpas-299, HL-60, and ML-2) as well as on normal human lymphocytes and on leukemic primary cells. SAHA induced dose-dependent and cell type-dependent cell death which displayed apoptotic features (caspase-3 activation and apoptotic DNA fragmentation) in most cell types including the normal lymphocytes. At subtoxic concentrations (0.5-1 microM), SAHA increased the cell adhesivity to fibronectin (FN) in all leukemia/lymphoma-derived cell lines but not in normal lymphocytes. This increase was accompanied by an enhanced expression of integrin beta1 and paxillin, an essential constituent of focal adhesion complexes, both at the protein and mRNA level. On the other hand, the inhibition of ROCK protein, an important regulator of cytoskeleton structure, had no consistent effect on SAHA-induced increase in the cell adhesivity. The promotion of cell adhesivity to FN seems to be specific for SAHA as we observed no such effects with other HDAC inhibitors (trichostatin A and sodium butyrate).
References provided by Crossref.org
Group I p21-activated kinases in leukemia cell adhesion to fibronectin
Adhesion structures in leukemia cells and their regulation by Src family kinases
