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Li et al. J Transl Genet Genom 2021;5:163-72 https://dx.doi.org/10.20517/jtgg.2021.22 Page 9

(hepatomegaly) without noticeable changes in liver function. In contrast, the changes in body weight gain
and organ weight after long-term dietary feeding of flavokawain A in TRAMP mice have not been observed
[16]
in our previous studies . Therefore, it is unlikely that flavokawain A is responsible for the reported “kava
hepatotoxicity”. Flavokawain A could be a safer product for cancer prevention than the KRE and the
kavalactone-rich kava fraction B.

In summary, the KRE product containing both kavalactones and flavokawains reduced the incidence of
HG-PIN and early-stage prostate adenocarcinoma and inhibited tumorigenesis. The KRE and kavalactone
weakly inhibited both MAO-A and LSD1 activities in prostate cancer, leading to their inhibitory effect on
AR signaling and cell proliferation. This study has provided a new knowledge basis for developing more
effective dual inhibitors of MAO-A and LSD1 enzymes for prostate cancer prevention and treatment.

DECLARATIONS
Acknowledgments
This work was supported in part by NIH awards 1R01CA193967-01A1 and DOD/Prostate Cancer Research
Program PC100869, and DOD/Prostate Cancer Research PC121803 (to Zi X).

Authors’ contributions
Conceived and designed study: Uchio E, Zi X
Analysed and interpreted data: Uchio E, Zi X
Drafted and revised the manuscript: Uchio E, Zi X
Performed experiments and the statistical analyses: Li X, Song L, Xu S, Tippin M, Meng S, Xie J
All authors read and approved the manuscript.

Availabilities of data and materials
The data that support the findings of this study are available from the corresponding author upon
reasonable request.

Financial support and sponsorship
This work was supported in part by NIH awards 1R01CA193967-01A1 and DOD/Prostate Cancer Research
Program PC100869, and DOD/Prostate Cancer Research PC121803 (to Zi X).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
The animal experiments were performed according to the approved protocol (#2007-2740) by University of
California, Irvine, Institutional Animal Care and Use Committee.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2021.

REFERENCES
1. Key Statistics for Prostate Cancer. Available from: https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. [Last
accessed on 3 Jun 2021].
2. Carlsson S, Benfante N, Alvim R, et al. Long-term outcomes of active surveillance for prostate cancer: the memorial sloan kettering
cancer center experience. J Urol 2020;203:1122-7. DOI PubMed PMC