The structure of chromatin is made up of dna, histones, and non-histone proteins with the basic repeating unit, nucleosome. the structure of chromatin can be reversibly modified in several ways including histone acetylation. histone acetyltransferases (hats) and histone deacetylases (hdacs) are two groups of enzymes that involved in acetylation and regulate gene expression. histone deacetylases have a key role in the remodeling of chromatin and the epigenetic regulation of gene expression. hdac inhibitors (hdacs) can inhibit hdacs and affect gene expression. hdac inhibitor valproic acid (vpa) has antitumor activities against certain cancers that make it an attractive drug for treating cancer. the aim of the present study was to analyze the effect of vpa on proliferation and apoptosis in colon cancer ht 29 cell line.
Materials and methods:
the cells were cultured at a density of 5 × 105 and treated with vpa to determine cell viability and flow cytometry. after 24, 48 and 72 h of treatment, mtt assay and flow cytometry assay were used to evaluate the viability and apoptotic effects of vpa.
Results: the result of mtt assay indicated that valproic acid significantly reduced the number of viable ht 29 cells in a time- and dose-dependent manner (p < 0.001) in all treatment groups by 28% to 86% at 24 h, 24% to 74% at 48 h and 18% to 64% at 72 h. ic50 value of vpa that inhibited 50% of the ht 29 cancer cell was 2.5 μm for 24 h (p˂0.001). the result of flow cytometry assay revealed that vpa induced significant apoptosis vs. control group in all treated groups. maximal and minimal apoptotic cell was observed in the groups which received vpa for 24 and 72 h respectively (p˂0.001).
Conclusion: vpa can significantly inhibit the growth and induce apoptosis in the ht 29 cancer cell line.
Keywords: valproic acid, proliferation, apoptosis, colon cancer