Mifepristone (RU486) is an orally effective progesterone (PR) receptor and glucocorticoid receptor (GR) antagonist used as an abortion drug with in vitro IC50 values of 0.2nM and 2.6nM, respectively [1]. Mifepristone is an antiprogestin that blocks the effects of progesterone, causing cervical and uterine vasodilation and uterine contractions [2]. Mifepristone can also be used to treat depression and improve neurocognitive function and mood [3].
In vitro, treatment of ovarian cancer SK-OV-3, OV2008, IGROV-1 and OV2008 cells with mifepristone (20μM) completely blocked cell growth at 24h, and the effect lasted for 3 days [4]. Treatment of human gastric adenocarcinoma MKN-45 cells with mifepristone (5, 10, 20μM) dose-dependently inhibited heterotypic adhesion of cells to matrix gel, accompanied by downregulation of integrin β3 expression in cells [5].
In vivo, oral treatment of C57BL/6 mice with mifepristone (200 mg/kg) for 1 week completely blocked the reduction in the CD4:CD8 T cell ratio in secondary lymphoid tissue (SLT) induced by enriched environment (EE)[6]. Mifepristone (25 mg/kg) treated by subcutaneous injection for 14 days in depression model rats improved interleukin 1β (IL-1β)-induced depressive-like behavior and regulated the function of microglia and astrocytes[7].
References:
[1] Jiang W, Allan G, Fiordeliso J J, et al. New progesterone receptor antagonists: phosphorus-containing 11β-aryl-substituted steroids[J]. Bioorganic & medicinal chemistry, 2006, 14(19): 6726-6732.
[2] Ashok P W, Wagaarachchi P T, Templeton A. The antiprogestogen mifepristone: a review[J]. Current Medicinal Chemistry-Immunology, Endocrine & Metabolic Agents, 2002, 2(2): 71-90.
[3] Young A H, Gallagher P, Watson S, et al. Improvements in neurocognitive function and mood following adjunctive treatment with mifepristone (RU-486) in bipolar disorder[J]. Neuropsychopharmacology, 2004, 29(8): 1538-1545.
[4] Goyeneche A A, Caron R W, Telleria C M. Mifepristone inhibits ovarian cancer cell growth in vitro and in vivo[J]. Clinical Cancer Research, 2007, 13(11): 3370-3379.
[5] Li D Q, Wang Z B, Bai J, et al. Effects of mifepristone on invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo[J]. World Journal of Gastroenterology: WJG, 2004, 10(12): 1726.
[6] Xiao R, Bergin S M, Huang W, et al. Environmental and genetic activation of hypothalamic BDNF modulates T-cell immunity to exert an anticancer phenotype[J]. Cancer immunology research, 2016, 4(6): 488-497.
[7] Zhang Y P, Wang H Y, Zhang C, et al. Mifepristone attenuates depression-like changes induced by chronic central administration of interleukin-1β in rats[J]. Behavioural brain research, 2018, 347: 436-445.