Synthesis, Spectral Characterization, and In Vitro Cellular Activities of Metapristone, a Potential Cancer Metastatic Chemopreventive Agent Derived from Mifepristone (RU486)
Journal Title: The AAPS Journal - Year 2014, Vol 16, Issue 2
Abstract
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.
Authors and Affiliations
Jichuang Wang, Jianzhong Chen, Liyuan Wan, Jingwei Shao, Yusheng Lu, Yewei Zhu, Minrui Ou, Suhong Yu, Haijun Chen, Lee Jia
Keywords
Related Articles
- EP ID EP681063
- DOI 10.1208/s12248-013-9559-2
- Views 71
- Downloads 0
Optimizing targeted gene delivery: Chemical modification of viral vectors and synthesis of artificial virus vector systems
In comparison to classical medicines, gene therapy has the potential to mediate the highest possible level of therapeutic specificity. Every normal or diseased cell can switch on or off a gene expression cassette in a ti...
Ligand Binding Assays in the 21st Century Laboratory: Automation
Many manufacturers offer well-designed instrument-specific authentication built into the automated system software. Instrument-specific security often contains thorough system tracking and audit trail generation for ensu...
Pocket-Based Drug Design: Exploring Pocket Space
The online version of this article (doi:10.1208/s12248-012-9426-6) contains supplementary material, which is available to authorized users.
Symbiotic relationship of pharmacogenetics and drugs of abuse
Pharmacogenetics/pharmacogenomics is the study of how genetic variation affects pharmacology, the use of drugs to treat disease. When drug responses are predicted in advance, it is easier to tailor medications to differe...
Role of Cannabinoids in the Development of Fatty Liver (Steatosis)
Emerging evidence suggests that cannabinoids play an important role in the modulation of fatty liver, which appears to be mediated via activation of cannabinoid receptors. Steatogenic agents such as ethanol and high-fat...