Impairment of prostate cancer cell growth by a selective and reversible lysine-specific demethylase 1 inhibitor

Dominica Willmann, Soyoung Lim, Stefan Wetzel, Eric Metzger, Anett Jandausch, Wolfram Wilk, Manfred Jung, Ignasi Forne, Axel Imhof, Andreas Janzer, Jutta Kirfel, Herbert Waldmann, Roland Schüle, Reinhard Buettner*

*Corresponding author for this work
92 Citations (Scopus)


Post-translational modifications of histones by chromatin modifying enzymes regulate chromatin structure and gene expression. As deregulation of histone modifications contributes to cancer progression, inhibition of chromatin modifying enzymes such as histone demethylases is an attractive therapeutic strategy to impair cancer growth. Lysine-specific demethylase 1 (LSD1) removes mono- and dimethyl marks from lysine 4 or 9 of histone H3. LSD1 in association with the androgen receptor (AR) controls androgen-dependent gene expression and prostate tumor cell proliferation, thus highlighting LSD1 as a drug target. By combining protein structure similarity clustering and in vitro screening, we identified Namoline, a γ-pyrone, as a novel, selective and reversible LSD1 inhibitor. Namoline blocks LSD1 demethylase activity in vitro and in vivo. Inhibition of LSD1 by Namoline leads to silencing of AR-regulated gene expression and severely impairs androgen-dependent proliferation in vitro and in vivo. Thus, Namoline is a novel promising starting compound for the development of therapeutics to treat androgen-dependent prostate cancer.

Original languageEnglish
JournalInternational Journal of Cancer
Issue number11
Pages (from-to)2704-2709
Number of pages6
Publication statusPublished - 01.12.2012


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