Changes in nuclear disorder strength (L_d) following VPA treatment.

<p><b>A)</b> Representative pseudocolor PWS images from nuclei of HT-29 and CSK constructs untreated or treated with 0.5 mM VPA. Color shows the magnitude of the <i>L_d</i> in an individual nucleus. <b>B)</b> Percent difference in combined nuclear <i>L_d</i> over experimental repeats in HT-29 and CSK knockdown cells. Nuclear <i>L_d</i> mostly decreased following VPA treatment in each cell line and to a greater extent in the CSK constructs. <b>C)</b> Percent difference in nuclear disorder strength between HT-29 and CSK constructs after each treatment. Treatment with higher concentrations of VPA (0.5 mM and 1.5 mM) nullified the nuclear <i>L_d</i> differences between the cell lines.</p

HDAC2 expression is up-regulated in human field carcinogenesis and early carcinogenesis.

<p><b>A)</b> mRNA expression of HDAC1, HDAC2, HDAC3, HDAC5, HDAC7 in human field carcinogenesis from (n = 86, patients with adenomas vs. controls). <b>B)</b> Representative TEM images of nuclei in histologically normal rectal cells from patients with or without adenomas elsewhere in the colon. <b>C)</b> Up-regulation of HDAC2 in field carcinogenesis was confirmed in human resection samples by qRT-PCR methods (n = 12, patients with adenomas vs. controls). <b>D)</b> Representative TEM images of saline-injected or azoxymethane-injected (AOM) nuclei obtained from the distal colon at a premalignant time point. <b>E)</b> HDAC2 expression is also up-regulated in the AOM (azoxymethane-injected) rat model for early colorectal carcinogenesis (n = 12 animals). Standard error bars shown with *<i>p</i><0.05.</p

HDAC inhibition differentially affects cell viability in colon cancer cell line variants.

<p><b>A)</b> TEM micrographs of chromatin structure in the HT-29 colon cancer cell line genetic variants, HT-29 control and CSK knockdown. <b>B)</b> HDAC2 expression is up-regulated in the CSK knockdown cell lines. <b>C)</b> MNase assay on HT-29 (H) and CSK knockdown (C) cells also indicate a more compact chromatin structure present in the CSK constructs. <b>D)</b> HT-29 and CSK knockdown cells in 96-well plates were treated with increasing concentrations of VPA for 24 h and then assayed for proliferation using standard WST-1 assay. Absorbance was measured after 20 min at 37°C. VPA treatment reduced cell viability in both cell lines, while the effect was greater in the CSK constructs. Standard error bars shown with *<i>p</i><0.05.</p