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

Jinhui Zhang, Lei Wang, Yong Zhang, Li Li, Suni Tang, Chengguo Xing, Sung Hoon Kim, Cheng Jiang, Junxuan Lü

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 (5mg/mouse, Monday-Friday) of AGN or vehicle, beginning at 8wk 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) (0.12g/mouse) than vehicle-treated counterparts (0.81g/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.

Original languageEnglish (US)
Pages (from-to)1567-1583
Number of pages17
JournalMolecular Carcinogenesis
Volume54
Issue number12
DOIs
StatePublished - Dec 2015

Fingerprint

Angelica
Neuroendocrine Carcinoma
Transgenic Mice
Prostate
Carcinogenesis
Adenocarcinoma
Fibroblast Growth Factor 2
Genes
Inflammation
Neoplasms
Messenger RNA
Tumor Microenvironment
Data Mining
Euthanasia
Angiogenesis Inducing Agents
Proteome
Tumor Suppressor Genes
Morphogenesis
Transcriptome
Heterografts

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Cite this

Zhang, Jinhui ; Wang, Lei ; Zhang, Yong ; Li, Li ; Tang, Suni ; Xing, Chengguo ; Kim, Sung Hoon ; Jiang, Cheng ; Lü, Junxuan. / Chemopreventive effect of Korean Angelica root extract on TRAMP carcinogenesis and integrative "omic" profiling of affected neuroendocrine carcinomas. In: Molecular Carcinogenesis. 2015 ; Vol. 54, No. 12. pp. 1567-1583.
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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 (5mg/mouse, Monday-Friday) of AGN or vehicle, beginning at 8wk 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) (0.12g/mouse) than vehicle-treated counterparts (0.81g/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.",
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Chemopreventive effect of Korean Angelica root extract on TRAMP carcinogenesis and integrative "omic" profiling of affected neuroendocrine carcinomas. / Zhang, Jinhui; Wang, Lei; Zhang, Yong; Li, Li; Tang, Suni; Xing, Chengguo; Kim, Sung Hoon; Jiang, Cheng; Lü, Junxuan.

In: Molecular Carcinogenesis, Vol. 54, No. 12, 12.2015, p. 1567-1583.

Research output: Contribution to journalArticle

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AU - Zhang, Jinhui

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AU - Xing, Chengguo

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AB - 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 (5mg/mouse, Monday-Friday) of AGN or vehicle, beginning at 8wk 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) (0.12g/mouse) than vehicle-treated counterparts (0.81g/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.

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