Effect of mifepristone on proliferation and apoptosis of Ishikawa endometrial adenocarcinoma cells.
OBJECTIVE
To determine the mechanism by which mifepristone improves breakthrough bleeding, the effects of mifepristone on proliferation and apoptosis of Ishikawa endometrial carcinoma cells were evaluated in the presence and absence of progestin.


METHODS
Prospective basic research study.


METHODS
Research laboratories for reproductive health at a university medical school.


METHODS
None.


METHODS
Ishikawa cells were cultured in vitro. Mifepristone and/or medroxyprogesterone acetate at various concentrations were added to the cells.


METHODS
Determination of cell proliferation and apoptosis.


RESULTS
Colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine (BrdU) labeling analysis demonstrated that mifepristone inhibited the growth of Ishikawa cells and percentage of BrdU-labeled cells in a time- and dose-dependent manner. Flow cytometry analysis demonstrated that mifepristone at 100 micromol/L, which completely inhibited cell proliferation, increased the proportion of cells in the S phase and diminished the cells in the G2/M phase. Apoptosis was identified by annexin-V-fluorescein isothiocyanate binding and caspase-3 activation. Immunofluorescent double labeling of Ishikawa cells in the absence or presence of mifepristone revealed that BAX protein expression increased and translocated from cytosol to mitochondria.


CONCLUSIONS
Mifepristone inhibited cell growth by arresting cell cycle progression at S phase, induced apoptosis through caspase-3 activation, and modulated apoptosis regulatory genes BCL2/BAX and FAS/FASLG in Ishikawa cells. Together, these data imply that the improvement in breakthrough bleeding observed with mifepristone might be due to diminished volume of endometrial tissue similar to that seen with endometrial atrophy.
Li
Aimin
A
Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Felix
Juan C
JC
Minoo
Parviz
P
Amezcua
Charles A
CA
Jain
John K
JK
D000230:Adenocarcinoma / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*
D015735:Mifepristone