title: 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.
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou, 350002, China; School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Chen
authors.forename: Jichuang
authors.initials: J
authors.lastname: Wang
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shao
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
authors.forename: Suhong
authors.initials: S
authors.lastname: Yu
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Liu
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D000021:Abortifacient Agents, Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000032:Abortion, Therapeutic; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D015735:Mifepristone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000473:pathology*
chemical_list: D000021:Abortifacient Agents, Steroidal; D015735:Mifepristone
keywords: cancer metastasis prevention; enterohepatic circulation; metapristone; mifepristone; terminating pregnancy