film was developed as per manufacturer’s instructions.All animal studies had been carried out in accordance together with the guidelines of the Institute for Animal Studies at the Albert Einstein College of Medicine

s of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR. Citation: Li X, Liu Z, Xu X, Blair CA, Sun Z, et al. Kava Components Down-Regulate Expression of AR and AR Splice Variants and Reduce Growth in PatientDerived Prostate Cancer Xenografts in Mice. PLoS ONE 7: e31213. doi:10.1371/journal.pone.0031213 Editor: Chad Creighton, Baylor College of Medicine, United States of America Received November 22, 2011; Accepted January 4, 2012; Published February 9, 2012 Copyright: 2012 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by National Institutes of Health grants CA129793 and CA122558 and American Institute for Cancer Research grant 41493. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. E-mail: [email protected] Current address: Department of Gastrointestinal Surgery, Guangzhou First Municipal People’s Hospital, Guangzhou, Guangdong Province, China Ethyl eicosapentaenoate citations Introduction Asian/Pacific men who consume a low fat and plant-based diet have the lowest rates of clinical PCa in the world. However, when Asian men migrate to the US, ” rates of clinical PCa increase. These observations implicate both environmental factors and dietary habits in PCa development. Therefore, one of strategies for prevention and treatment of PCa has focused on the use of natural and synthetic bioactive food components. Kava is a perennial plant indigenous to the Pacific Islands. Kava root and rhizome are used to prepare a non-fermented and ceremonial beverage with relaxant effects in the Pacific Islands for thousands of years. Unusually low incidences of several cancers, including lung and prostate cancer, are reported in the Pacific Island nations despite a high portion of smokers in these populations. In addition, Steiner 21799757” reported that the age-standardized cancer incidence for the three highest kava-drinking countries was one fourth or one third that of non-kava-drinking countries, such as New Zealand and United States, and non-kava-drinking Polynesians. Uniquely, in these three kava-drinking countries more men drink kava and smoke than do women, yet there is a lower incidence of cancer for men than for women. Moreover, the Cancer Council’s Cancer in New South Wales Migrants 1991 2001 report found that the PCa incidence in Fijian men who migrated to and were resident in NSW, Australia, increased by 5.1 times compared to those living in Fiji. This report has prompted us to investigate the potential benefits of kava extracts and its active components for PCa prevention. We report for the first time that a commercial kava extract and its active components downregulate AR expression. Depletion of AR protein occurred through two different mechanisms: 1) enhanced AR protein degradation, and 2) reduced Specificity protein 1 -mediated February 2012 | Volume 7 | Issue 2 | e31213 Kava Root Extracts and Prostate Cancer AR transcription. Kava extract and flavokawain B treatment of mice with patient-derived xenografts reduced tumor growth and expression of AR and its target genes in tumor tissues, and lowered serum PSA levels. MTT assay Cells were plated at a de