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Cancer Prevention Research
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Research Article

Interception Targets of Angelica Gigas Nakai Root Extract versus Pyranocoumarins in Prostate Early Lesions and Neuroendocrine Carcinomas in TRAMP Mice

Su-Ni Tang, Peixin Jiang, Sangyub Kim, Jinhui Zhang, Cheng Jiang and Junxuan Lü
Su-Ni Tang
1School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas.
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Peixin Jiang
1School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas.
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Sangyub Kim
2Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania.
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Jinhui Zhang
1School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas.
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Cheng Jiang
1School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas.
2Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania.
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Junxuan Lü
1School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas.
2Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania.
3Penn State Cancer Institute, Pennsylvania State University, Hershey, Pennsylvania.
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  • For correspondence: jxl1140@psu.edu
DOI: 10.1158/1940-6207.CAPR-20-0589
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Abstract

We reported efficacy of Angelica gigas Nakai (AGN) root ethanol extract and equimolar decursin (D)/decursinol angelate (DA) through daily gavage starting at 8 weeks of age (WOA) to male transgenic adenocarcinoma of mouse prostate (TRAMP) mice such that these modalities suppressed precancerous epithelial lesions in their dorsolateral prostate (DLP) to similar extent, but AGN extract was better than the D/DA mixture at promoting the survival of mice bearing prostate neuroendocrine carcinomas to 28 WOA. Here, we compared by microarray hybridization the mRNA levels in pooled DLP tissues and individual neuroendocrine carcinomas to characterize potential molecular targets of AGN extract and D/DA. Clustering and principal component analyses supported distinct gene expression profiles of TRAMP DLP versus neuroendocrine carcinomas. Pathway Enrichment, Gene Ontology, and Ingenuity Pathway Analyses of differential genes indicated that AGN and D/DA affected chiefly processes of lipid and mitochondrial energy metabolism and oxidation-reduction in TRAMP DLP, while AGN affected neuronal signaling, immune systems and cell cycling in neuroendocrine carcinomas. Protein–Protein Interaction Network analysis predicted and reverse transcription-PCR verified multiple hub genes common in the DLP of AGN- and D/DA-treated TRAMP mice at 28 WOA and select hub genes attributable to the non-D/DA AGN components. The vast majority of hub genes in the AGN-treated neuroendocrine carcinomas differed from those in TRAMP DLP. In summary, the transcriptomic approach illuminated vastly different signaling pathways and networks, cellular processes, and hub genes of two TRAMP prostate malignancy lineages and their associations with the interception efficacy of AGN and D/DA.

Prevention Relevance: This study explores potential molecular targets associated with in vivo activity of AGN root alcoholic extract and its major pyranocoumarins to intercept precancerous epithelial lesions and early malignancies of the prostate. Without an ethically-acceptable, clearly defined cancer initiation risk reduction strategy available for the prostate, using natural products like AGN to delay formation of malignant tumors could be a plausible approach for prostate cancer prevention.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).

  • Prior presentation: Preliminary data analyses were communicated at the American Association for Cancer Research (AACR) annual meeting in 2015 (abstract no. 1907. Su-Ni Tang, et al, “Transcriptomic signatures associated with the efficacy of Angelica gigas (AGN) ethanol extract and its pyranocoumarins on two lineages of carcinogenesis in TRAMP mice”).

  • Cancer Prev Res 2021;XX:XX–XX

  • Received November 11, 2020.
  • Revision received January 19, 2021.
  • Accepted February 26, 2021.
  • Published first March 1, 2021.
  • ©2021 American Association for Cancer Research.

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This OnlineFirst version was published on April 8, 2021
doi: 10.1158/1940-6207.CAPR-20-0589

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Interception Targets of Angelica Gigas Nakai Root Extract versus Pyranocoumarins in Prostate Early Lesions and Neuroendocrine Carcinomas in TRAMP Mice
Su-Ni Tang, Peixin Jiang, Sangyub Kim, Jinhui Zhang, Cheng Jiang and Junxuan Lü
Cancer Prev Res April 8 2021 DOI: 10.1158/1940-6207.CAPR-20-0589

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Interception Targets of Angelica Gigas Nakai Root Extract versus Pyranocoumarins in Prostate Early Lesions and Neuroendocrine Carcinomas in TRAMP Mice
Su-Ni Tang, Peixin Jiang, Sangyub Kim, Jinhui Zhang, Cheng Jiang and Junxuan Lü
Cancer Prev Res April 8 2021 DOI: 10.1158/1940-6207.CAPR-20-0589
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Cancer Prevention Research
eISSN: 1940-6215
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