In vitro and in vivo efficacy and safety evaluation of metapristone and mifepristone as cancer metastatic chemopreventive agents

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Jichuang WangLee Jia

Abstract

Malignant melanoma, the most deadly form of skin cancer, has a high propensity for metastatic spread and is notoriously chemotherapy-resistant. Metapristone is the primary metabolite of mifepristone (RU486) and shows biological activities similar to RU486. In the present study, we comprehensively investigated the efficacy of metapristone as a metastatic chemopreventive against melanoma B16F10 cells in vitro and in vivo, and evaluated the safety profile of both drugs in mice. Metapristone showed less cytostatic effect in vitro and in vivo in comparison with mifepristone. However, metapristone interfered the adhesion of B16F10 cells to fibronectin by down-regulating cellular expression of integrin α4. Chemopreventive pretreatment followed by oral administration of metapristone and mifepristone (2.5, 10, 50 mg/kg/day for 35 days) to melanoma C57BL/6 mouse model showed significant attenuation of pulmonary metastatic development. Oral administration of high doses of metapristone and mifepristone to normal mice for 35 days (25, 100, 250 mg/kg/day) resulted in a dose-dependent increase in mouse liver weight that was more severe with mifepristone than metapristone. The long-term toxicity study revealed more changes by mifepristone in c...Continue Reading

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Citations

May 9, 2019·Therapeutic Apheresis and Dialysis : Official Peer-reviewed Journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy·Mevlut CeriMurat Duranay
Oct 15, 2020·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·L A CasulariR Maggi
Mar 31, 2021·Acta Pharmacologica Sinica·Xin-Peng YaoHui-Chang Bi

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