Abstract

Abstract Kava kava has been traditionally used to prepare beverages and herbal medicines in the Pacific Islands. Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. To determine the chemopreventive efficacy of kava root extracts, TRAMP mice were fed with commercial kava root extract supplemented food. In the prevention protocol, TRAMP mice were fed with 3 or 6 g (0.3% or 0.6%) kava root extract /kg food starting at 6 weeks of age and ending at 12 weeks of age, resulting in decreased numbers of high-grade prostatic intraepithelial neoplasia and moderately differentiated adenocarcinomas in kava root extract fed mice compared to the mice fed with control food (p<0.01). In the intervention protocol, in which TRAMP mice were fed with 0.3% or 0.6% kava root extract food starting at 6 weeks of age and ending at 24 weeks of age, the average genitourinary (GU) weight of 0.6% kava root extract fed mice was significantly reduced when compared to control food fed mice (1.98±2.07 gram vs.3.63±4.28 gram, p<0.05, Mann-Whitney U and Kolmogorov-Smirnov test). The percentages of large tumors (GU weight > 0.9 gram) were also decreased from 86.4% in the control group to 52.2% and 43.5% in 0.3 and 0.6 % kava food groups, respectively. In addition, we showed that kawain, the main component of kava root extracts, inhibited LSD1 enzyme activity, enhanced H3K9 dimethylation and decreased the mRNA expression of androgen receptor target genes, including PSA and TMPRSS2, in LNCaP cells. Taken together, these results suggested that dietary consumption of kava products have the potential to reduce the risk of prostate cancer development. Citation Format: Xuesen Li, Christopher A. Blair, Xiaolin Zi. Dietary feeding of Kava root extract inhibits prostate carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2141. doi:10.1158/1538-7445.AM2014-2141

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