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.

DESIGN: Laboratory research.

SETTING: Academic medical center.

PATIENT(S): Premenopausal women (n = 12) undergoing hysterectomy for leiomyoma-related symptoms.

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

MAIN OUTCOME MEASURE(S): 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.

RESULT(S): 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.

CONCLUSION(S): CDB4124 selectively inhibits proliferation and induces apoptosis in LSM but not in MSM cells.