Histone Deacetylase Inhibition and Dietary Short-Chain Fatty Acids
Figure 1
Snapshot of the effects of histone deacetylase inhibitors (HDACi) in human cells. (a) Chemical structures of sodium butyrate (NaB), Trichostatin A (TSA), and suberoylanilide hydroxamic acid (SAHA). (b) HDACi result in the hyperacetylation of histones. Immunoblots of acetylated histone H3 and loading control GAPDH in human peripheral blood monocyte cells treated with and without NaB and TSA at the indicated concentrations for 24 hours prior to whole cell lysate extraction. (c) HDACi decrease cell viability in (i) K562 cells and (ii) HT29 cells. Cells were treated with NaB, TSA, and SAHA with the indicated concentrations for 24 hours and relative cell viability was measured using the Cell Titre assay kit (Promega). (d) HDACi induce apoptosis (caspase 3/7 activity) in (i) K562 cells and (ii) HT29 cells. Cells were treated with and without HDACi for 24 hours and caspase 3/7 activity was measured using the Apo-one assay kit (Promega). (e) NaB alters the cell cycle distribution of K562 cells. Cells were either (i) untreated or treated with 10 mM NaB for 24 hours prior to staining with propidium iodide and analysis for cell cycle distribution using flow cytometry. (f) Sodium butyrate augments doxorubicin-induced DNA double-strand breaks (H2AX foci) in K562 cells. Cells were treated with and without 10 mM NaB for 24 hours prior to one-hour incubation with 1 μM doxorubicin. Cells were washed and incubated in fresh media for a further 24 hours and stained for H2AX. Images were acquired using a Ziess 510 Meta confocal microscope and analyzed using ImageJ. (g) Photomicrographs indicating H2AX in K562 cells treated with doxorubicin or a combination of the anthracycline with NaB.
