title: Metapristone (RU486 derivative) inhibits cell proliferation and migration as melanoma metastatic chemopreventive agent.
abstract: Uncontrolled cell proliferation and metastasis are the two well-known manifestations of melanoma. We hypothesized that metapristone, a potential cancer metastatic chemopreventive agent derived from mifepristone (RU486), had a dual function to fight cancer. In the present study, our findings clearly demonstrated that metapristone had modest cytostatic effect in melanoma cells. Metapristone inhibited cell viability and induced both early and late apoptosis in B16F10 and A375 cells in a time- and concentrate-dependent manner. Metapristone-treatment caused the cell arrest at the G0/G1 stage, and the inhibition of colony formation in B16F10 cells. Western blot analysis further revealed that metapristone treatment elicited a decline of Akt and ERK phosphorylation and Bcl-2, and facilitated expression of total P53 and Bax in A375 cells. In addition, cell migration and invasion were significantly suppressed by metapristone through down-regulating the expression of MMP-2, MMP-9, N-cadherin and vimentin, whereas up-regulating E-cadherin expression. Notably, metapristone exhibited anti-metastatic activity in melanoma B16F10 cells in vivo. Our results reveal metapristone, having the dual function of anti-proliferation and anti-migration for melanoma cell lines, may be a useful chemopreventive agent to reduce the risk of melanoma cancer metastasis.
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350002, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350002, China.
authors.forename: Jiahang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350002, China.
authors.forename: Weiqun
authors.initials: W
authors.lastname: Liu
authors.affiliation: Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, Fujian Medical University, Fuzhou, Fujian 350108, China.
authors.forename: Jichuang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350002, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350002, China. Electronic address: pharmlink@gmail.com.
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015735:Mifepristone; C000592521:metapristone
keywords: Cancer metastasis; Chemopreventive agent; Melanoma cells; Metapristone; Mifepristone (RU486); Pro-apoptosis