Gene expression signatures associated with suppression of TRAMP prostate carcinogenesis by a kavalactone-rich Kava fraction

• Published in: Molecular carcinogenesis Vol. 55; no. 12; pp. 2291 - 2303
• Main Authors: Tang, Su-Ni, Zhang, Jinhui, Jiang, Peixin, Datta, Palika, Leitzman, Pablo, O'Sullivan, M. Gerard, Jiang, Cheng, Xing, Chengguo, Lü, Junxuan
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.12.2016; Wiley Subscription Services, Inc
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Carcinogenesis - drug effects; Carcinogenesis - genetics; Carcinogenesis - pathology; Cell cycle; Cell growth; Female; Fractions; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Kava - chemistry; Kava kavalactone rich fraction; Lactones - chemistry; Lactones - pharmacology; Lactones - therapeutic use; Male; Mice; Mice, Inbred C57BL; neuroendocrine carcinoma; Piper methysticum; Prostate - drug effects; Prostate - metabolism; Prostate - pathology; Prostate cancer; prostate epithelial lesions; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Rodents; TRAMP; Transcriptome - drug effects; Transgenes; neuroendocrine carcinoma; Kava kavalactone rich fraction; TRAMP; prostate epithelial lesions
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.22469

Kava (Piper methysticum Forster) extract and its major kavalactones have been shown to block chemically induced lung tumor initiation in mouse models. Here we evaluated the chemopreventive effect of a kavalactone‐rich Kava fraction B (KFB), free of flavokavains, on carcinogenesis in a transgenic adenocarcinoma of mouse prostate (TRAMP) model and characterized the prostate gene expression signatures. Male C57BL/6 TRAMP mice were fed AIN93M diet with or without 0.4% KFB from 8 wk of age. Mice were euthanized at 16 or 28 wk. The growth of the dorsolateral prostate (DLP) lobes in KFB‐treated TRAMP mice was inhibited by 66% and 58% at the respective endpoint. Anterior and ventral prostate lobes in KFB‐treated TRAMP mice were suppressed by 40% and 49% at 28 wk, respectively. KFB consumption decreased cell proliferation biomarker Ki‐67 and epithelial lesion severity in TRAMP DLP, without detectable apoptosis enhancement. Real time qRT‐PCR detection of mRNA from DLP at 28 wk showed decreased expression of cell cycle regulatory genes congruent with Ki‐67 suppression. Microarray profiling of DLP mRNA indicated that “oncogene‐like” genes related to angiogenesis and cell proliferation were suppressed by KFB but tumor suppressor, immunity, muscle/neuro, and metabolism‐related genes were upregulated by KFB in both TRAMP and WT DLP. TRAMP mice fed KFB diet developed lower incidence of neuroendocrine carcinomas (NECa) (2 out of 14 mice) than those fed the basal diet (8 out of 14 mice, χ2 = 5.6, P < 0.025). KFB may, therefore, inhibit not only TRAMP DLP epithelial lesions involving multiple molecular pathways, but also NECa. © 2016 Wiley Periodicals, Inc.