Histone deacetylase inhibitors induce growth inhibition, cell cycle arrest and apoptosis in human choriocarcinoma cells.
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-diphenyl-tetrazolium 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.
Takai
Noriyuki
N
Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Hasama-machi, Yufu-shi, Oita 879-5593, Japan. takai@med.oita-u.ac.jp
Ueda
Tami
T
Nishida
Masakazu
M
Nasu
Kaei
K
Narahara
Hisashi
H
D000107:Acetylation / Q000187:drug effects; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011419:Propidium / Q000378:metabolism
D017304:Annexin A5; D051017:Apoptosis Regulatory Proteins; D015820:Cadherins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D011419:Propidium