Suberoylanilide hydroxamic acid (SAHA) at subtoxic concentrations increases the adhesivity of human leukemic cells to fibronectin.
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).
Kuzelová
Katerina
K
Department of Cellular Biochemistry, Institute of Hematology and Blood Transfusion, Prague, Czech Republic. kuzel@uhkt.cz
Pluskalová
Michaela
M
Brodská
Barbora
B
Otevrelová
Petra
P
Elknerová
Klára
K
Grebenová
Dana
D
Hrkal
Zbynek
Z
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002469:Cell Separation; D005353:Fibronectins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D019012:Integrin beta1 / Q000378:metabolism; D007938:Leukemia / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D051419:Paxillin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077337:Vorinostat
D000970:Antineoplastic Agents; D005353:Fibronectins; D006877:Hydroxamic Acids; D019012:Integrin beta1; D051419:Paxillin; D000077337:Vorinostat