RU486-induced growth inhibition of human endometrial cells

• Published in: Fertility and sterility Vol. 74; no. 5; pp. 1014 - 1019
• Main Authors: Murphy, Ana A, Zhou, Mimi H, Malkapuram, Srividya, Santanam, Nalini, Parthasarathy, Sampath, Sidell, Neil
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2000; Elsevier Science
• Subjects: antioxidants; Antioxidants - pharmacology; antiprogesterone; Biological and medical sciences; Cell Division - drug effects; Cell Line; endometriosis; endometrium; Endometrium - cytology; Endometrium - drug effects; Female; Genital system. Reproduction; Hormone Antagonists - pharmacology; Humans; Medical sciences; mifepristone; Mifepristone - analogs & derivatives; Mifepristone - pharmacology; Pharmacology. Drug treatments; Pregnatrienes - pharmacology; RU486; endometrium; endometriosis; antiprogesterone; mifepristone; RU486; antioxidants; Human; Cell proliferation; Endometriosis; Antihormone; Antioxidant; Cell differentiation; In vitro; Biological activity; Female genital diseases; Transfection; Uterus; Antiprogesterone; Female genital system; Established cell line; Uterine diseases; Female; Mifepristone; Antimitotic; Endometrium
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/S0015-0282(00)01606-X

Objective: To determine the direct action of RU486 on endometrial cell proliferation and to differentiate whether the antioxidant or the antiprogesterone property of RU486 is predominately responsible for its effect on cell growth. Design: In vitro study comparing the effects of RU486 (antiprogesterone and antioxidant), reduced RU486 (antioxidant), ZK112,993 (antiprogesterone), and lazaroid U74,500A (antioxidant) on endometrial cell growth. The human endometrial cell line EM42 was used in transient transfection assays to confirm the relative antiprogesterone potency of the various compounds. Setting: Academic medical center Patient(s): Women presenting with pelvic pain or infertility and diagnosed with endometriosis at time of surgery or women desiring tubal ligation with a normal pelvis (controls). Intervention(s): Endometrial cell cultures were treated with RU486, reduced RU486, lazaroid U74,500A, and ZK112,993. Main Outcome Measure(s): Tritiated thymidine incorporation was used to assess cell growth. Inhibition of progesterone induction of transiently transfected reporter plasmids was used to measure antiprogesterone activity of compounds studied. Result(s): RU486 reduced cell growth in a dose-dependent fashion of the endometrial cell lines EM42 and RL95-2 and of endometrial and endometriosis cells from primary culture. After being reduced, RU486 lost most of its antiprogesterone activity but retained its antiproliferative properties. ZK112,993 was similar in potency to RU486 as a progesterone antagonist but did not significantly modify endometrial cell growth. Lazaroid U74,500A was devoid of antiprogesterone activity but was shown to be a potent antiproliferative agent. Conclusion(s): RU486 has a direct inhibitory effect on human endometrial cell growth. This activity appears to be at least partly mediated through its antioxidant property.