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 and kavalactones showed a significant inhibition of LSD1 and MAO-A enzyme activities.Conclusion:Our results suggest that consumption of kava products through diet can delay prostate cancer development and progression and that kavalactones may be a new structure model for developing a potent dual inhibitor of LSD1 and MAO-A.
Highlights
Prostate cancer has a projected incidence of ~248,530 new cases diagnosed, accounting for ~34,130 deaths in 2021 in the United States, ranking the second leading cause of cancer death in men[1]
Our results suggest that consumption of kava products through diet can delay prostate cancer development and progression and that kavalactones may be a new structure model for developing a potent dual inhibitor of lysine-specific demethylase 1 (LSD1) and monoamine oxidase A (MAO-A)
We have previously shown that oral administration of kava root extracts (KRE) through dietary supplementation effectively reduced the growth of patient-derived xenograft (PDX) tumors and down-regulated the protein levels of androgen receptor (AR) and the expression of AR target genes prostate-specific antigen (PSA) and transmembrane protease, serine 2 (TMPRESS2)[9]
Summary
Prostate cancer has a projected incidence of ~248,530 new cases diagnosed, accounting for ~34,130 deaths in 2021 in the United States, ranking the second leading cause of cancer death in men[1]. Over one-third of prostate cancer is slowly growing or progressing over several decades This group of patients without cancer-related symptoms do not warrant aggressive, immediate treatment[2]. Instead, they are closely monitored for their indolent status using prostate-specific antigen (PSA) kinetics, periodic biopsies for histologic progression, and possibly surveillance magnetic resonance imaging (MRI) until further treatment is needed as judged by physicians. They are closely monitored for their indolent status using prostate-specific antigen (PSA) kinetics, periodic biopsies for histologic progression, and possibly surveillance magnetic resonance imaging (MRI) until further treatment is needed as judged by physicians This emergent strategy for the management of indolent prostate cancer is called active surveillance[2]. Very few chemopreventive agents are effective for their testing in chemoprevention studies in this population
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
