Synergistic Induction of Apoptosis in Primary B-CLL Cells after Treatment with Recombinant Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Histone Deacetylase Inhibitors
HDAC inhibition by Oxam and TSA leads to TRAIL receptor expression on B-CLL cells. (a). The percentages of B-CLL cells expressing TRAIL-R1 or TRAIL-R2 are shown. B-CLL cells were cultured for 16 hours in the presence or absence of individual HDACi, as indicated, then analyzed by flow cytometry for TRAIL-R1 and TRAIL-R2 surface expression. Filled grey histogram = Isotype control, dotted line = untreated, solid line = HDACi. (b) Enriched PBMC from healthy donors were cultured for 16 hours as indicated, then the surface expression levels of TRAIL-R1 and TRAIL-R2 were analyzed by flow cytometry. Filled histogram = Isotype control, dotted line = untreated, solid line = vehicle alone or HDACi. Numbers indicate the percentages of positively staining cells, compared to isotype. (c) TRAIL-R1 and TRAIL-R2 mRNA levels in B-CLL cultured as indicated for 16 hours. (d) The percentages of B-CLL cells expressing surface TRAIL-R1 or TRAIL-R2 in response to varying doses of TSA are given. Filled histogram = Isotype control, dotted line = untreated, solid line = vehicle alone or HDACi. For all panels, one experiment, representative of at least 5 experiments using cells from different donors, is shown.