RRC ID 45138
Author Uzawa K, Kasamatsu A, Shimizu T, Saito Y, Baba T, Sakuma K, Fushimi K, Sakamoto Y, Ogawara K, Shiiba M, Tanzawa H.
Title Suppression of metastasis by mirtazapine via restoration of the Lin-7C/β-catenin pathway in human cancer cells.
Journal Sci Rep
Abstract No definitive therapy exists to treat human metastatic tumors. We reported previously that down-regulation of Lin-7C is essential for metastasis of human squamous cell carcinomas (hSCCs). In this study, we investigated the chemical restoration of Lin-7C expression and demonstrated its effectiveness for suppressing the metastatic potential in human cancer cells. Ingenuity Pathway Analysis (IPA) identified candidate chemical agents, i.e., apomorphine, caffeine, risperidone, quetiapine, and mirtazapine. Among them, mirtazapine, an antagonist of HTR2C, an upstream molecule of Lin-7C, caused substantial up-regulation of the Lin-7C/β-catenin pathway in a metastatic hSCC cell line and human melanoma-derived cell line in vitro, and up-regulation did not contribute to cellular proliferation. Moreover, the antimetastatic effect of mirtazapine in these metastatic cell lines in vivo also was evident in multiple organs of immunodeficient mice with no marked side effects. The current data offer novel information for further study of antimetastatic activity in association with enhanced Lin-7C/β-catenin pathway activation with mirtazapine.
Volume 4
Pages 5433
Published 2014-6-25
DOI 10.1038/srep05433
PII srep05433
PMID 24961284
PMC PMC4069674
MeSH Adrenergic alpha-Antagonists / pharmacology Animals Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism Cell Line, Tumor Cell Movement / drug effects Cell Movement / genetics Gene Expression Regulation, Neoplastic / drug effects Humans Immunoblotting Melanoma / drug therapy Melanoma / genetics Melanoma / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism* Mianserin / analogs & derivatives* Mianserin / pharmacology Mice, Inbred BALB C Mice, Nude Mirtazapine Neoplasm Metastasis Neoplasms / drug therapy* Neoplasms / genetics Neoplasms / metabolism Receptor, Serotonin, 5-HT2C / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects* Signal Transduction / genetics Xenograft Model Antitumor Assays beta Catenin / genetics beta Catenin / metabolism*
IF 3.998
Times Cited 7
Human and Animal Cells SAS(RCB1974) G-361(RCB0991)