Synthesis, spectral characterization, and in vitro cellular activities of metapristone, a potential cancer metastatic chemopreventive agent derived from mifepristone (RU486).
Mifepristone (RU486) is marketed and used widely by women as an abortifacient, and experimentally for psychotic depression and anticancer treatments. After administration, metapristone is found to be the most predominant metabolite of mifepristone. We hypothesized that adhesion of circulating tumor cells (CTCs) to vascular endothelial bed is a crucial starting point in metastatic cascade, and that metapristone can serve as a cancer metastatic chemopreventive agent that can interrupt adhesion and invasion of CTCs to the intima of microvasculature. In the present study, we modified the synthesis procedure to produce grams of metapristone, fully characterized its spectral properties and in vitro cellular activities, including its cytostatic effects, cell cycle arrest, mitochondrial membrane potential, and apoptosis on human colorectal cancer HT-29 cells. Metapristone concentration dependently interrupted adhesion of HT-29 cells to endothelial cells. Metapristone may potentially be a useful agent to interrupt metastatic initiation.
Cancer Metastasis Alert and Prevention Center, College of Chemistry and Chemical Engineering, Fuzhou University, 523 Industry Road, Science Building, 3FL, Fuzhou, Fujian, 350002, China.
Jichuang
J
Wang
Jianzhong
J
Chen
Liyuan
L
Wan
Jingwei
J
Shao
Yusheng
Y
Lu
Yewei
Y
Zhu
Minrui
M
Ou
Suhong
S
Yu
Haijun
H
Chen
Lee
L
Jia
D017304:Annexin A5 / Q000378:metabolism; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015735:Mifepristone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D017550:Spectroscopy, Fourier Transform Infrared
D017304:Annexin A5; D016588:Anticarcinogenic Agents; D015735:Mifepristone; D053148:Caspase 3; C000592521:metapristone