Abstract LB-184: A paradigm of carcinogenesis lineage specificities of cancer chemoprevention: Korean Angelica extract and its pyranocoumarins in the transgenic adenocarcinoma of mouse prostate model.
Authors: Tang Suni , Zhang Yong , Jiang Peixin , Zhang Jinhui , Xing Chengguo , Kim Sung-Hoon , Jiang Cheng , Lu Junxuan 
Published: August 2014

Abstract
Oriental medicinal herbals hold great promise for low cost and non-toxic chemopreventive remedies for cancers of prostate and other organs. Rigorous efficacy assessment in preclinical models of prostate carcinogenesis is necessary and essential for evidence-based “translational” preventive oncology with such herbal natural products. Our international collaborative team had recently shown Korean Angelica gigas Nakai (AGN) ethanolic extract with anti-cancer efficacy in a number of xenograft or allograft cancer models. However the active chemical species and cellular and molecular targets remain to be identified. In the present study we aim to test the hypothesis that orally administered AGN extract or its major pyranocoumarin compounds decursin/decursinol angelate (D/DA) inhibit prostatic carcinogenesis in the well-characterized C57BL/6 transgenic adenocarcinoma of mouse prostate (TRAMP) mice as the preclinical model. Previous studies by us (The Prostate, 2011) and others have suggested a new paradigm of distinct lineages of carcinogenesis in this model: i.e., androgen receptor (AR)-dependent glandular epithelial lesions (usually arise from the dorsal-lateral prostate [DLP] lobes) and AR-independent neuroendocrine (NE)-like poorly differentiated (PD) carcinomas (usually from the ventral prostate [VP] lobes). Experimentally, 3 cohorts of male C57BL/6 TRAMP mice (35-36 mice per group) were fed AIN93M purified diet and gavaged with either 0.15 mL of vehicle (Ethanol: PEG400: Tween 80: 5% glucose = 3:6:1:20), AGN (5 mg per mouse) or D/DA (3 mg per mouse, equi-molar to that in AGN) 5 days per week from 8 weeks of age (WOA). Mice were euthanized at either 16 WOA (n=12 mice per group) or 28 WOA unless large tumors necessitated earlier sacrifice. The results show that the growth of the TRAMP DLP lobes in AGN- and D/DA-treated mice were inhibited by 71% and 61%, respectively (ANOVA, P&lt;0.0001), from vehicle-control mice by 16 WOA. By 28 WOA, the inhibition of TRAMP DLP growth was 73% and 75%, respectively (ANOVA, P&lt;0.001). Whereas AGN decreased the burden of palpable prostate tumors (i.e., NE-Ca), D/DA did not. In summary, AGN extract and equi-molar intake of D/DA inhibit epithelial lineage lesions, the extract is much superior to D/DA compounds at suppressing NE-carcinogenesis, lending credence to the lineage specific targeting hypothesis. Future work will focus on 1) identifying non-pyranocoumarin compounds in AGN extract that inhibit NE-carcinogenesis; 2) testing whether D/DA-hydrolysis product decursinol mediates the epithelial targeting inhibitory action. Supported by NCCAM AT 005383 R21 and AT007395 R01 grants.
Citation Format: Suni Tang, Yong Zhang, Peixin Jiang, Jinhui Zhang, Chengguo Xing, Sung-Hoon Kim, Cheng Jiang, Junxuan Lu. A paradigm of carcinogenesis lineage specificities of cancer chemoprevention: Korean Angelica extract and its pyranocoumarins in the transgenic adenocarcinoma of mouse prostate model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-184. doi:10.1158/1538-7445.AM2013-LB-184