Anticancer activity of MS-275, a novel histone deacetylase inhibitor, against human endometrial cancer cells.
BACKGROUND
Histone deacetylase inhibitors (HDACIs) can inhibit cell proliferation, induce cell cycle arrest and stimulate apoptosis of cancer cells.


METHODS
The effects of a novel HDACI, MS-275, on 4 endometrial cancer cell lines and normal human endometrial epithelial cells was investigated. Endometrial cancer cells were treated with various concentrations of MS-275 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 assays showed that all endometrial cancer cell lines were sensitive to the growth inhibitory effect of MS-275, although the normal endometrial epithelial cells were viable after treatment with the same doses of MS-275 that induced growth inhibition in endometrial cancer cells. The cell cycle analysis indicated that their exposure to MS-275 induced the G0/G1 arrest 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.


CONCLUSIONS
These results raise the possibility that MS-275 may prove particularly effective in the treatment of endometrial cancer.
Takai
Noriyuki
N
Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita, Japan. takai@med.oita-u.ac.jp
Ueda
Tami
T
Nishida
Masakazu
M
Nasu
Kaei
K
Narahara
Hisashi
H
D000107:Acetylation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D011725:Pyridines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D011725:Pyridines; C118739:entinostat