Format

Send to

Choose Destination
  • Filters activated: Field: Title Word. Clear all
Mol Carcinog. 2015 Dec;54(12):1567-83. doi: 10.1002/mc.22230. Epub 2014 Oct 12.

Chemopreventive effect of Korean Angelica root extract on TRAMP carcinogenesis and integrative "omic" profiling of affected neuroendocrine carcinomas.

Author information

1
Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas.
2
Hormel Institute, University of Minnesota, Austin, Minnesota.
3
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota.
4
Cancer Preventive Material Development Research Center and Institute, College of Oriental Medicine, Kyunghee University, Seoul, Republic of Korea.

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.

KEYWORDS:

Angelica gigas Nakai; TRAMP model; microarray; prostate cancer; proteomics; transcriptomics

PMID:
25307620
PMCID:
PMC4872417
DOI:
10.1002/mc.22230
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center