The effects of histone deacetylase inhibitor valproic acid on endometrial cell proliferation

In this research, we investigated the possible effects of histone deacetylase inhibitor valproic acid (VAP) during the proliferative phase of the mestrual cycle that is stimulated by estrogen, on an in-vitro endometrium model, by using immunocytochemistry methodIn order to observe the effects of VAP on cell proliferation, we treated the cells with different concentrations of VAP alone, or in combination with 17-ß-estradiol. Cell viability was determined by trypan blue dye exclusion. A decrease in cell viability percentage was determined that it was due to different concentrations. The S-phased Ishikawa cells were visualized by staining with anti-Bromodeoxyuridine (BrdU) antibody. Significant cell cycle regulatory proteins p21 and p53 expressions were analyzed. It was observed that 17-ß-estradiol increased the cell proliferation. VAP treatment decreased and/or inhibited the proliferation rates of the cells in a dose-dependent manner. 20 mM VAP treatment inhibited the cell proliferation and induced p21 and p53 protein expressions. The characteristic morphological changes and caspase-3 expression of apoptotic cell death were also observed at this concentration. It was determined that 50 mM VAP treatment inhibited the cell proliferation but p21 and p53 protein expressions did not occur. In addition, no morphological features of apoptosis or caspase-3 expression were observed at high doseThe present data has shown us that HDAC inhibitor VAP can inhibit the endometrial cell proliferation and induce cell death. In the light of these findings, the identification of VAP suggests a potential role to be used as a therapeutic agent in the treatment of endometrium-derived diseases; such as endometrial neoplasms or endometriosis.