PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells
Figure 4
PCI-24781 induces a caspase-dependent increase in both total and acetylated histone H3 protein expressions. Jurkat cells were treated with 0.5 M of PCI-24781, with or without pretreatment of (a) 24 mM NAC, (b) 1 mM buthionine sulfoximine (BSO), (c) 50 M zVAD-fmk or IETD-fmk, for 30 minutes. After 16 hours of incubation, samples were either harvested to determine DNA fragmentation by PI staining or lysed for western blot. Acetylated histone H3, total histone H3, and actin were measured by western blot. (d) Jurkat and I9.2 cells were treated with or without 0.5 M PCI-24781 and incubated for 16 hours. Lysates were harvested and lysed. Acetylated histone H3, total histone H3, and actin were measured by western blot. (e) Jurkat and I2.1 cells were treated with or without 0.25 or 0.5 M PCI-24781 and incubated for 16 hours. Samples were harvested and lysed. Acetylated histone H3, total histone H3, and actin were measured by western blot. For Figures 4(a)–4(d), results are representative of at least two independent experiments.
