title: Chemopreventive effect of Korean Angelica root extract on TRAMP carcinogenesis and integrative "omic" profiling of affected neuroendocrine carcinomas.
abstract: Angelica gigas Nakai (AGN) root ethanol extract exerts anti-cancer activity in several allograft and xenograft models. Here we examined its chemopreventive efficacy through gavage administration against primary carcinogenesis in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Male C57BL/6 TRAMP mice and wild type littermates were given a daily gavage (5 mg/mouse, Monday-Friday) of AGN or vehicle, beginning at 8 wk of age (WOA). All mice were terminated at 24 WOA, unless earlier euthanasia was necessitated by large tumors. Whereas AGN-treated TRAMP mice decreased dorsolateral prostate lesion growth by 30% (P = 0.009), they developed fewer and smaller neuroendocrine-carcinomas (NE-Ca) (0.12 g/mouse) than vehicle-treated counterparts (0.81 g/mouse, P = 0.037). We analyzed the proteome and transcriptome of banked NE-Ca to gain molecular insights. Angiogenesis-antibody array detected a substantial reduction in AGN-treated NE-Ca of basic fibroblast growth factor (FGF2), an angiogenesis stimulator. iTRAQ proteomics plus data mining suggested changes of genes upstream and downstream of FGF2 functionally consistent with AGN inhibiting FGF2/FGFR1 signaling at different levels of the transduction cascade. Moreover, AGN upregulated mRNA of genes related to immune responses, restored expression of many tumor suppressor genes, and prostate function and muscle differentiation genes. On the other hand, AGN down-regulated mRNA of genes related to neuron signaling, oncofetal antigens, inflammation, and mast cells, Wnt signaling, embryonic morphogenesis, biosynthesis, cell adhesion, motility, invasion, and angiogenesis. These changes suggest not only multiple cancer cell targeting actions of AGN but also impact on the tumor microenvironments such as angiogenesis, inflammation, and immune surveillance.
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas.
authors.forename: Suni
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Chengguo
authors.initials: C
authors.lastname: Xing
authors.affiliation: Cancer Preventive Material Development Research Center and Institute, College of Oriental Medicine, Kyunghee University, Seoul, Republic of Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas.
authors.forename: Junxuan
authors.initials: J
authors.lastname: Lü
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D029969:Angelica / Q000737:chemistry*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy*; D018890:Chemoprevention / Q000379:methods; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D020543:Proteome / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D010936:Plant Extracts; D020543:Proteome
keywords: Angelica gigas Nakai; TRAMP model; microarray; prostate cancer; proteomics; transcriptomics