Histone deacetylase inhibitors induce growth inhibition, cell cycle arrest and apoptosis in human choriocarcinoma cells

Abstract

Abstract.We investigated the effect of five histone deacetylase inhibitors (HDACIs) on the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of five HDACIs, and their effects on cell growth, cell cycle, apoptosis, and related measurements were investigated. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that the BeWo choriocarcinoma cell line was sensitive to the growth inhibitory effect of five HDACIs. Cell cycle analysis indicated that exposure to HDACIs decreased the proportion of cells in the S-phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and loss of the transmembrane potential of mitochondria. This induction occurred in concert with altered expression of genes related to cell growth, malignant phenotype, and apoptosis. Furthermore, HDACI treatment of this cell line increased acetylation of H3 and H4 histone tails. These results raise the possibility that HDACIs may prove particularly effective in the treatment of choriocarcinoma.

The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells and modulates autoimmunity in NZB/W F1 mice

“…Numerous studies have shown HDIs reduce the proliferation and exert pro-apoptotic effects on cellular function of transformed cells in vitro and in vivo [4,20,21]. Additionally, HDIs reduce inflammatory mediator production [22,23].…”

Preclinical Studies on Histone Deacetylase Inhibitors as Therapeutic Reagents for Endometrial and Ovarian Cancers

“…A study by Takai et al . demonstrated both antiproliferative and proapoptotic activities of HDAC inhibitors in human OC cells [65]. Furthermore, soft agar colony formation assays and 3-4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide MTT assays showed that many endometrial and ovarian cancer cell lines were sensitive to the growth inhibitory effect of HDAC inhibitors, although normal endometrial epithelia were viable after the treatment with the same concentrations of HDAC inhibitors.…”

Transient exposure to sodium butyrate after germinal vesicle breakdown improves meiosis but not developmental competence in pig oocytes

“…Covalent histone modification is involved in the regulation of acetylation, methylation, phosphorylation, ubiquitination and sumoylation (Kouzarides, 2007). Acetylation affects many fundamental processes and an increase in histone acetylation is always followed by cell‐cycle arrest, differentiation or apoptosis (Senese et al, 2007; Takai et al, 2008; Frew et al, 2009). During oocyte IVM, histone acetylation and phosphorylation are dramatically altered (Wang et al, 2006).…”