The selective progesterone receptor modulator CDB4124 inhibits proliferation and induces apoptosis in uterine leiomyoma cells.

Abstract

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.

• Authors: Xia Luo, Ping Yin, John S Coon V, You-Hong Cheng, Ronald D Wiehle, Serdar E Bulun
• Journal: Fertility and sterility (Fertil Steril) Vol. 93 Issue 8 Pg. 2668-73 (May 15 2010) ISSN: 1556-5653 [Electronic] United States
• PMID: 20056218 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• Cell Cycle Proteins
• KLF11 protein, human
• Norpregnadienes
• Proliferating Cell Nuclear Antigen
• Proto-Oncogene Proteins c-bcl-2
• Receptors, Progesterone
• Repressor Proteins
• telapristone acetate
• Poly(ADP-ribose) Polymerases

Topics

• Adult
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins
• Cell Cycle Proteins (biosynthesis)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Female
• Humans
• Leiomyoma (pathology)
• Middle Aged
• Myometrium (drug effects)
• Norpregnadienes (pharmacology)
• Poly(ADP-ribose) Polymerases (drug effects, metabolism)
• Proliferating Cell Nuclear Antigen (biosynthesis)
• Proto-Oncogene Proteins c-bcl-2
• Receptors, Progesterone (drug effects)
• Repressor Proteins (biosynthesis)
• Uterine Neoplasms (pathology)