The heat map demonstrates that both vorinostat and LBH589 segregated independently from the vehicle treated controls in both cell lines. However, the cluster sellekchem tree generated also demonstrates that while vorinostat and LBH589 segregate from the vehicle treated controls, they demonstrate very similar clustering patterns indicat ing that they induce similar transcriptional response within each cell line. Differentially expressed genes in response to HDACi treatment To compare the effects of HDACi treatment relative to vehicle treated cells, Venn analysis was utilized. In HCT116 cells, a combined total of 3566 genes were mod ulated by HDACi treatment representing approximately 7% of the total gene set ana lyzed by the array.

Within this set, 3100 DEGs were iden tified following vorinostat treatment of which 57 genes were uniquely modulated by vorinostat treatment as illus trated by the Venn diagram. Following treat ment with LBH589, 3509 DEGs were identified of which 466 genes were uniquely modulated by LBH589. This data demonstrates that in HCT116 cells, vorino stat and LBH589 exert similar effects on gene expression with 85% of all DEGs modulated in a consistent manner by both vorinostat and LBH589 treatment. In HT29 cells, 2645 genes were modulated in total by both HDACi representing approximately 5% of the total gene set analyzed by the array. Of this total, 2448 genes were modulated by vorinostat of which 216 of these DEGs were unique only to vorinostat treatment. Following treatment with LBH589, 2429 genes were modulated of which 197 were unique transcrip tional responses to LBH589 not observed with vorinostat treatment.

This indicates that there is also sig nificant similarity in the transcriptional changes induced by vorinostat and LBH589 in HT29 cells with 75% of the total DEG set common transcriptional changes in response to either HDACi. Of the 3100 DEGs modulated Drug_discovery by vorinostat treatment in HCT116 cells, 24 were up regulated and 17 were down regulated 2 fold. Of the 3509 genes modulated follow ing treatment with LBH589 in HCT116 cells, 92 genes were upregulated and 150 were downregulated 2 fold. The top 15 up and downregulated genes modulated 2 fold for both vorionostat and LBH589 treatment in HCT116 cells are displayed in Table 1. Similarly, in HT29 cells, the majority of DEGs were also modulated 2 fold when compared to vehicle treated controls as was observed in the HCT116 cells.

Of the 2448 DEGs modulated by vorinostat treatment in HT29 cells, 138 were up regulated and 53 were down regulated 2 fold. Of the 3509 genes modulated following treatment with LBH589 in HT29 Brefeldin A protein transport cells, 163 genes were upregulated and 54 were downregulated 2 fold. The top 15 up and downregulated genes for both vorinostat and LBH589 treatment in HT29 cells are displayed in Table 2.