Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer

Figure 2 Pre-treatment regime with histone deacetylase inhibitor maximally enhances binding of chemotherapeutic drugs to chromatin. A: (a) Immunoblot analysis for the comparison of site-specific histone acetylation levels between gastric cancer (GC) cell lines, transformed AGS and untransformed HFE145; (b) Nucleo-cytosolic fractions were used to compare HDAC levels in GC cell lines using calorimetric assays; and (c) Real time PCR data of Class I to Class IV HDAC levels in the AGS cell line compared to HFE145 (^aP < 0.05; ^bP < 0.009, ^cP < 0.0009, ^dP < 0.0001); B: Schematic representation of three different combination regimes: (a) concurrent [histone deacetylase inhibitor (HDACi) + Drug], (b) pre- (HDACi Drug) and (c) post- (Drug HDACi); C: AGS cells were treated with chemotherapeutic drugs and HDACi at their inhibitory concentration (IC)50 concentration for 24 h in three different combinations as mentioned above. Experiment was performed in triplicate, absorbance was taken, normalized with blank, and mean absorbance was incorporated into a bar graph. HDACi: Histone deacetylase inhibitor; HDAC: Histone deacetylase; Drug: Chemotherapy drugs; VPA: Valproic acid; SAHA: Suberoylanilide hydroxamic acid; TSA: Trichostatin A; IC: Inhibitory concentration.