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Li et al. J Transl Genet Genom 2021;5:163-72 Journal of Translational
DOI: 10.20517/jtgg.2021.22
Genetics and Genomics

Original Article Open Access

Kava root extracts hinder prostate cancer
development and tumorigenesis by involvement of

dual inhibition of MAO-A and LSD1

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1,2
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Xuesen Li , Liankun Song , Shan Xu , Matthew Tippin , Shuan Meng , Jun Xie , Edward Uchio , Xiaolin
Zi 1,2,3
1
Department of Urology, University of California, Irvine, Orang, CA 92868, USA.
2
Chao Family Comprehensive Cancer Center, University of California, Orange, CA 92868, USA.
3
Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92617, USA.
Correspondence to: Prof. Xiaolin Zi, Department of Urology, University of California, Irvine, 101 The City Drive South, Rt.81
Bldg.55 Rm.204, Orange, CA 92868, USA. E-mail: xzi@uci.edu
How to cite this article: Li X, Song L, Xu S, Tippin M, Meng S, Xie J, Uchio E, Zi X. Kava root extracts hinder prostate cancer
development and tumorigenesis by involvement of dual inhibition of MAO-A and LSD1. J Transl Genet Genom 2021;5:163-72.
https://dx.doi.org/10.20517/jtgg.2021.22
Received: 14 Apr 2021 First Decision: 14 May 2021 Revised: 16 May 2021 Accepted: 25 May 2021 First online: 28 May 2021
Academic Editor: Sanjay Gupta Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

Abstract
Aim: Here, we aim to evaluate the chemopreventive efficacy of kava root extracts (KRE) in transgenic
adenocarcinoma of the mouse prostate (TRAMP) mice and investigate potential molecular targets of kavalactones,
the main components of kava.

Methods: TRAMP mice were administrated with KRE formulated food for different periods of time, and then the
incidences of high-grade prostatic intraepithelial neoplasia (HG-PIN) and adenocarcinomas and tumor burdens
were compared between vehicle control and KRE food fed groups. In addition, the inhibitory effect of the KRE and
kavalactones on monoamine oxidase A (MAO-A) and lysine-specific demethylase 1 (LSD1) enzyme activities were
examined by commercially available inhibitor screening kits. Histone H3 lysine 9 dimethylation was also evaluated
in prostate cancer cells and tumor tissues using Western blotting analysis.

Results: Dietary feeding of 0.3% and 0.6% KRE to TRAMP mice from ages of 6 weeks to 12 weeks inhibited HG-
PIN by 43.5% and 59.7%, respectively, and prostate adenocarcinoma by 53.5% and 66.4%, respectively. In
addition, 0.6% KRE fed TRAMP mice from ages of 6 weeks to 24 weeks exhibited a significant reduction of
genitourinary weight (a surrogate of tumor burden) by 54.5% and reduced body weight gain. Furthermore, the KRE

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
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adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
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indicate if changes were made.

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