title: Suppression of metastasis by mirtazapine via restoration of the Lin-7C/β-catenin pathway in human cancer cells.
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.
authors: 1] Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan [2] Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors: Katsuhiro
authors: K
authors: Uzawa
authors: Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors: Atsushi
authors: A
authors: Kasamatsu
authors: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Toshihiro
authors: T
authors: Shimizu
authors: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Yasuhiro
authors: Y
authors: Saito
authors: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Takao
authors: T
authors: Baba
authors: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Kentaro
authors: K
authors: Sakuma
authors: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Kazuaki
authors: K
authors: Fushimi
authors: Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors: Yosuke
authors: Y
authors: Sakamoto
authors: Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors: Katsunori
authors: K
authors: Ogawara
authors: 1] Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan [2] Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Masashi
authors: M
authors: Shiiba
authors: 1] Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan [2] Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors: Hideki
authors: H
authors: Tanzawa
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000078785:Mirtazapine; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000317:Adrenergic alpha-Antagonists; C119588:LIN-7 protein, mammalian; D008565:Membrane Proteins; D044405:Receptor, Serotonin, 5-HT2C; D051176:beta Catenin; D008803:Mianserin; D000078785:Mirtazapine