CBHA is a family of hybrid polar compounds that inhibit histone deacetylase, and induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells.
OBJECTIVE
We investigated the effect of a novel synthesized histone deacetylase inhibitor (HDACI), CBHA, on three endometrial cancer cell lines, two ovarian cancer cell lines, and normal human endometrial epithelial cells.


METHODS
Endometrial and ovarian cancer cells were treated with various concentrations of CBHA, and its effect on cell growth, cell cycle, apoptosis, and related measurements was investigated.


RESULTS
The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that all endometrial and ovarian cancer cell lines were sensitive to the growth-inhibitory effect of CBHA, although normal endometrial epithelial cells were viable after treatment with the same doses of CBHA that induced growth inhibition in endometrial and ovarian cancer cells. Cell cycle analysis indicated that their exposure to CBHA decreased the proportion of cells in the S-phase and increased the proportion in the G(0)/G(1) 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, CBHA treatment of these cell lines increased acetylation of H3 and H4 histone tails.


CONCLUSIONS
These results raise the possibility that CBHA may prove particularly effective in the treatment of endometrial and ovarian cancers.
Takai
Noriyuki
N
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Japan. takai@med.oita-u.ac.jp
Ueda
Tami
T
Nishida
Masakazu
M
Nasu
Kaei
K
Matsuda
Kaho
K
Kusumoto
Mamiko
M
Narahara
Hisashi
H
D000107:Acetylation / Q000187:drug effects; D017304:Annexin A5; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000494:pharmacology*; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006131:Growth Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010641:Phenotype; D010718:Phosphatidylserines / Q000032:analysis
D017304:Annexin A5; D000970:Antineoplastic Agents; D002934:Cinnamates; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D056572:Histone Deacetylase Inhibitors; D010718:Phosphatidylserines; C111238:carboxycinnamic acid bishydroxamide