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イツミ モモエ
逸見 百江 所属 川崎医科大学 医学部 一般教養 自然科学 職種 助教 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | High-throughput screen identifies 5-HT receptor as a modulator of AR and a therapeutic target for prostate cancer. |
| 掲載誌名 | 正式名：The Prostate 略 称：Prostate ISSNコード：10970045/02704137 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 80(11),pp.885-894 |
| 著者・共著者 | Momoe Itsumi, Masaki Shiota, Yohei Sekino, Miho Ushijima, Eiji Kashiwagi, Ario Takeuchi, Junichi Inokuchi, Shunichi Kajioka, Takeshi Uchiumi, Masatoshi Eto |
| 発行年月 | 2020/08 |
| 概要 | BACKGROUND:Eradication of persistent androgen receptor (AR) activity in castration-resistant prostate cancer may be a promising strategy to overcome castration resistance. We aimed to identify novel compounds that inhibit AR activity and could be potential therapeutic agents for prostate cancer.METHODS:A high-throughput screening system involving cell lines stably expressing AR protein and AR-responsive luciferase was employed for the 1260 compound library. Molecular and antitumor effects on candidate pathways that interacted with AR signaling were examined in prostate cancer cells expressing AR.RESULTS:The high-throughput screening identified various potential compounds that interfered with AR signaling through known and novel pathways. Among them, a 5-hydroxytryptamine 5A (5-HT5A) receptor antagonist suppressed AR activity through protein kinase A signaling, which was confirmed by 5-HT5A receptor knockdown. Consistently, 5-HT5A receptor inhibitors showed cytotoxic effects toward prostate cancer cells.CONCLUSIONS:Taken together, this study identifies 5-HT5A receptor as a promising therapeutic target for prostate cancer via its interaction with AR signaling. |
| DOI | 10.1002/pros.24022 |
| PMID | 32483877 |