Histone deacetylase inhibitors (HDACIs) can inhibit cell proliferation, induce cell cycle arrest, and stimulate the apoptosis of
cancer cells. We investigated the effects of a novel HDACI,
Scriptaid, on the Ishikawa
endometrial cancer cell line, SK-OV-3
ovarian cancer cell line, and normal human endometrial epithelial cells. Endometrial and
ovarian cancer cells were treated with various concentrations of
Scriptaid, and its effect on cell growth, cell cycle, apoptosis, and related measurements was investigated.
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that all endometrial and
ovarian cancer cell lines were sensitive to the growth inhibitory effect of
Scriptaid, although normal endometrial epithelial cells were viable
after treatment with the same doses of
Scriptaid that induced the growth inhibition of endometrial and
ovarian cancer cells. Cell cycle analysis indicated that their exposure to
Scriptaid decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 and/or G2/M 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 the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. Furthermore,
Scriptaid treatment of these cell lines increased acetylation of H3 and H4
histone tails. These results raise the possibility that
Scriptaid may prove particularly effective in the treatment of endometrial and
ovarian cancers.