The selective progesterone receptor modulator CDB4124 inhibits proliferation and induces apoptosis in uterine leiomyoma cells.
OBJECTIVE
To evaluate the effects of selective P receptor (PR) modulator CDB4124 on cell proliferation and apoptosis in cultured human uterine leiomyoma smooth muscle (LSM) cells and control myometrial smooth muscle (MSM) cells in matched uteri.


METHODS
Laboratory research.


METHODS
Academic medical center.


METHODS
Premenopausal women (n = 12) undergoing hysterectomy for leiomyoma-related symptoms.


METHODS
Treatment of primary LSM and MSM cells with CDB4124 (10(-8)-10(-6) M) or vehicle for 24, 48, or 72 hours.


METHODS
Western blot for protein expression of proliferating cell nuclear antigen, cleaved polyadenosine 5'-diphosphate-ribose polymerase, Bcl-2, and Krüppel-like transcription factor 11; 93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate viable cell numbers; and real-time polymerase chain reaction (PCR) to quantify messenger RNA (mRNA) levels.


RESULTS
Treatment with CDB4124 significantly decreased levels of the proliferation marker proliferating cell nuclear antigen, the number of viable LSM cells, and the antiapoptotic protein Bcl-2. On the other hand, treatment with CDB4124 increased levels of the apoptosis marker cleaved polyadenosine 5'-diphosphate-ribose polymerase and the tumor suppressor Krüppel-like transcription factor 11 in a dose- and time-dependent manner in LSM cells. In matched MSM cells, however, CDB4124 did not affect cell proliferation or apoptosis.


CONCLUSIONS
CDB4124 selectively inhibits proliferation and induces apoptosis in LSM but not in MSM cells.
Luo
Xia
X
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Yin
Ping
P
Coon V
John S
JS
Cheng
You-Hong
YH
Wiehle
Ronald D
RD
Bulun
Serdar E
SE
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000473:pathology*; D008875:Middle Aged; D009215:Myometrium / Q000187:drug effects; D009649:Norpregnadienes / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D011980:Receptors, Progesterone / Q000187:drug effects*; D012097:Repressor Proteins / Q000096:biosynthesis; D014594:Uterine Neoplasms / Q000473:pathology
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C115117:KLF11 protein, human; D009649:Norpregnadienes; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D011980:Receptors, Progesterone; D012097:Repressor Proteins; C461063:telapristone acetate; D011065:Poly(ADP-ribose) Polymerases