Abstract 2133: Suppressing effect of a Kava fraction on two lineages of prostate carcinogenesis in the transgenic adenocarcinoma of mouse prostate model

Abstract

Abstract Kava (Piper methysticum Forest) is a crop historically originating from west Pacific Islands. The epidemiologic studies for Pacific Island populations indicated that their cancer incidence rates were inversely related to the local consumptions of kava. Whereas chemopreventive efficacy of Kava ethanol extract has been shown in chemically-induced lung carcinogenesis models, its efficacy against prostate carcinogenesis is not known. In this study, we aim to evaluate the efficacy of Kava Fraction B, which is mostly kavalactones and free of flavokawains and most potent in lung carcinogenesis models, on prostatic carcinogenesis in the well-characterized C57BL/6 transgenic adenocarcinoma of mouse prostate (TRAMP) preclinical model. Previous studies by us (The Prostate, 2011) and others have suggested a paradigm of distinct lineages of carcinogenesis in this model: i.e., at least, androgen receptor (AR)-dependent glandular epithelia lesions (usually arise from the dorsal-lateral prostate [DLP] lobes) and AR-independent neuroendorine (NE)-like poorly differentiated (PD) carcinomas (usually derive from the ventral prostate [VP] lobe). Experimentally, male C57BL/6 TRAMP mice were fed AIN93M purified diet without or with 0.4% of Kava fraction B from 8 weeks of age (WOA). Mice were euthanized at either 16 WOA or 28 WOA unless large tumors necessitated earlier sacrifice. The growth of the DLP in Kava-treated TRAMP mice were inhibited by 70% (P<0.05) from control TRAMP mice by 16 WOA. By 28 WOA, the inhibition of TRAMP DLP growth were 76% (P<0.001). Furthermore, Kava-fed TRAMP mice cohort had lower incidence of palpable and dissectable tumors (2 out of 14 mice) than control mice (7 out of 14 mice). Therefore, Kava fraction B appeared to inhibit both epithelial lineage lesions and NE-carcinogenesis. Future work will focus on 1) profiling cellular processes and molecular targets of Kava fraction B and 2) identifying active compounds in Kava Fraction B that inhibit epithelial lineage lesions and NE-carcinogenesis. Supported in part by NCCAM AT007395 R01 and NCI CA142649 R01 grants. Citation Format: Su-Ni Tang, Palika Datta, Peixin Jiang, Pablo Leitzman, Cheng-guo Xing, Cheng Jiang, Junxuan Lu. Suppressing effect of a Kava fraction on two lineages of prostate carcinogenesis in the transgenic adenocarcinoma of mouse prostate 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 2133. doi:10.1158/1538-7445.AM2014-2133