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Synthesis, Spectral Characterization, and In Vitro Cellular Activities of Metapristone, a Potential Cancer Metastatic Chemopreventive Agent Derived from Mifepristone (RU486)

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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.

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Acknowledgements

These studies were supported by grants from the National Science Foundation of China Nos. 81201709, J1103303 and 81273548. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. 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 Wang, Jianzhong Chen, Liyuan Wan, Jingwei Shao, Yusheng Lu, Yewei Zhu, Minrui Ou, Suhong Yu, Haijun Chen & Lee Jia

  2. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350108, China

    Jianzhong Chen

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  1. Jichuang Wang
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Correspondence to Jingwei Shao or Lee Jia.

Additional information

Jichuang Wang and Jianzhong Chen These authors equally contributed to the work.

The study was presented in part at the 2013 annual meeting of American Association of Pharmaceutical Scientists, Antonio, TX, USA; November, 2013.

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Wang, J., Chen, J., Wan, L. et al. Synthesis, Spectral Characterization, and In Vitro Cellular Activities of Metapristone, a Potential Cancer Metastatic Chemopreventive Agent Derived from Mifepristone (RU486). AAPS J 16, 289–298 (2014). https://doi.org/10.1208/s12248-013-9559-2

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  • DOI: https://doi.org/10.1208/s12248-013-9559-2

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