The Unique Pharmacological Characteristics of Mifepristone (RU486): From Terminating Pregnancy to Preventing Cancer Metastasis

Abstract

Mifepristone (RU486) is a born-for-woman molecule discovered three decades ago. Unlike those antihypertensive and antipsychotic pharmaceutical blockbusters, this abortifacient offers relatively low profit potential. Current understanding of mechanism of action of mifepristone and its on-going clinical trials are changing our views on the drug beyond its abortifacient scope. Here we briefly review its metabolism and pharmacokinetic properties including its unique enterohepatic circulation, its mechanisms of actions involving antiprogesterone and antiglucocorticoid, growth inhibition of various cancer cell lines, suppression of invasive and metastatic cancer potential, downregulation of Cdk2, Bcl-2, and NF-kappa B, interference of heterotypic cell adhesion to basement membrane, and cell migration. We comprehensively analyze recent results from preclinical and clinical studies using mifepristone as an anticancer drug for breast, meningioma, and gliomas tumors in the central nervous system, prostate cancer, ovarian and endometrial cancer, and gastric adenocarcinoma. Although mifepristone has more benefits for global public health than we originally thought, its effect as a postmetastatic chemotherapeutic agent is limited. Nonetheless, owing to its unique safe, metabolism and other pharmacological properties, metapristone (the primary metabolite of mifepristone) may have potential for cancer metastatic chemoprevention.

Mifepristone Inhibits the Migration of Cervical Cancer Cells by Inhibiting Exocrine Secretion

“…Mifepristone was demonstrated to inhibit the migration of endometrial cancer cells through regulating H19 methylation [15,16]. In this study, the CC cell line, HeLa, was utilized.…”

“…Metapristone (MIF) was reported to suppress the proliferation or migration of cells in several cancer types, such as gliomas tumors in the central nervous system, prostate cancer, and ovarian andendometrial cancer [15,16]. However, whether MIF can affect exosome secretion to regulate cancer cell migration is poorly studied.…”

The Architecture and Function of Monoclonal Antibody‐Functionalized Mesoporous Silica Nanoparticles Loaded with Mifepristone: Repurposing Abortifacient for Cancer Metastatic Chemoprevention

“…[ 14 ] After being used by millions of women, and recently by men, for more than three decades, large amounts of preclinical and clinical information have been generated for this agent. The information clearly indicates that the compound has many more benefi ts for global public health than what we originally thought.…”

“…In preclinical oncology studies and clinical trials, MIF was reported to have a potent anti-proliferative effect on cancer cell lines derived from various tumors with a good safety profi le (doses ranging from 1 to 1500 mg per patient for a period ranging from 1 to 168 months, depending on the type of disease). [ 14 ] Our systems pharmacology analysis revealed 47 hub targets of MIF for cancer chemotherapy and potential metastasis chemoprevention. [ 15 ] The uniqueness of this compound lies on its long-lasting half-time in blood [ 16 ] due to, partially, its enterohepatic circulation as we analyzed by using systems pharmacokinetics.…”

A structural perspective on nuclear receptors as targets of environmental compounds

“…The synthetic steroid compound mifepristone (RU-486) is known for its antagonistic properties on the steroid receptors GR and PR and is primarily used for early termination of pregnancy; additionally, it displays an anti-diabetic effect and appears to be a promising drug for the treatment of certain cancers [80] . RU-486 and its metabolites can be found in the aquatic environment and should be considered as contaminants [81] .…”