NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses prostate cancer without adverse effect

Toshiki Etani; Takayoshi Suzuki; Taku Naiki; Aya Naiki-Ito; Ryosuke Ando; Keitaro Iida; Noriyasu Kawai; Keiichi Tozawa; Naoki Miyata; Kenjiro Kohri; Satoru Takahashi

doi:10.18632/oncotarget.3067

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Research Papers:

NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses prostate cancer without adverse effect

Toshiki Etani, Takayoshi Suzuki _, Taku Naiki, Aya Naiki-Ito, Ryosuke Ando, Keitaro Iida, Noriyasu Kawai, Keiichi Tozawa, Naoki Miyata, Kenjiro Kohri and Satoru Takahashi

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Oncotarget. 2015; 6:2865-2878. https://doi.org/10.18632/oncotarget.3067

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Abstract

Toshiki Etani1, Takayoshi Suzuki2, Taku Naiki1, Aya Naiki-Ito3, Ryosuke Ando1, Keitaro Iida1, Noriyasu Kawai1, Keiichi Tozawa1, Naoki Miyata4, Kenjiro Kohri1 and Satoru Takahashi3

1 Department of Nephro-Urology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan

2 Department of Chemistry, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan

3 Department of Experimental Pathology and Tumor Biology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan

4 Institute of Drug Discovery Science, Nagoya City University, Graduate School of Pharmaceutical Sciences, Nagoya, Japan

Correspondence:

Taku Naiki, email:

Takayoshi Suzuki, email:

Keywords: LSD1, epigenetics, prostate cancer, autophagy

Received: September 02, 2014 Accepted: December 22, 2014 Published: December 26, 2014

Abstract

Herein, we investigated therapeutic potential of a novel histone lysine demethylase 1 (LSD1) inhibitor, NCL1, in prostate cancer. Hormone-sensitive prostate cancer cells, (LNCaP) and castration resistant cancer cells (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. ChIP analysis showed that NCL1 induced H3K9me2 accumulation at the promoters of androgen-responsive genes. 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. In conclusion, NCL1 effectively suppressed prostate cancer growth without adverse events. We suggest that NCL1 is a potential therapeutic agent for hormone-resistant prostate cancer.

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Research Papers:

NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses prostate cancer without adverse effect

Abstract