Analysis of effectiveness of NCL1, a highly selective lysine-specific demethylase 1 inhibitor, for prostate cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 26861284
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: ETANI TOSHIKI 名古屋市立大学, 医学(系)研究科(研究院), 研究員 (30600754)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: エピジェネティクス / ヒストン修飾 / LSD1 / 前立腺癌 / オートファジー

Outline of Final Research Achievements

We investigated therapeutic potential of a novel histone lysine demethylase 1 (LSD1) inhibitor, NCL1, in prostate cancer. Prostate cancer cells, LNCaP, PC3 and PCai1 were treated with NCL1, and LSD1 expression and cell viability were assessed. Prostate cancer cells showed strong LSD1 expression, and cell viability was decreased by NCL1. NCL1 also induced G1 cell cycle arrest and apoptosis. In addition, autophagosomes and autolysosomes were induced by NCL1 treatment in LNCaP. Furthermore, LC3-II expression was significantly increased by NCL1 and chloroquine. In mice injected subcutaneously with PCai1 and intraperitoneally with NCL1, tumor volume was reduced with no adverse effects in NCL1-treated mice. Finally, LSD1 expression in human cancer specimens was significantly higher than that in normal prostate glands. NCL1 effectively suppressed prostate cancer growth without adverse events. We suggest that NCL1 is a potential therapeutic agent for hormone-resistant prostate cancer.

Free Research Field

医学