@article{3d0e360327c7402497512ec1965160a8,
title = "High-throughput screen identifies 5-HT receptor as a modulator of AR and a therapeutic target for prostate cancer",
abstract = "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.",
author = "Momoe Itsumi and Masaki Shiota and Yohei Sekino and Miho Ushijima and Eiji Kashiwagi and Ario Takeuchi and Junichi Inokuchi and Shunichi Kajioka and Takeshi Uchiumi and Masatoshi Eto",
note = "Funding Information: This study was supported by a JSPS KAKENHI grant (17K11145), and a Research Promotion Grant from the Japanese Urological Association. We are grateful to Dr. Martin Gleave (Vancouver Prostate Centre, Vancouver, BC, Canada) for providing the C4-2 cells, and Otsuka Pharmaceutical (Tokyo, Japan) for providing the AR-EcoScreen cells. We would like to thank Ms. Noriko Hakoda and Ms. Eriko Gunshima for technical assistance, and Alison Sherwin, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript. Funding Information: This study was supported by a JSPS KAKENHI grant (17K11145), and a Research Promotion Grant from the Japanese Urological Association. We are grateful to Dr. Martin Gleave (Vancouver Prostate Centre, Vancouver, BC, Canada) for providing the C4‐2 cells, and Otsuka Pharmaceutical (Tokyo, Japan) for providing the AR‐EcoScreen cells. We would like to thank Ms. Noriko Hakoda and Ms. Eriko Gunshima for technical assistance, and Alison Sherwin, PhD, from Edanz Group ( www.edanzediting.com/ac ) for editing a draft of this manuscript. Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals LLC",
year = "2020",
month = aug,
day = "1",
doi = "10.1002/pros.24022",
language = "English",
volume = "80",
pages = "885--894",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "11",
}
