title: Chemopreventive Effects of Korean Angelica versus Its Major Pyranocoumarins on Two Lineages of Transgenic Adenocarcinoma of Mouse Prostate Carcinogenesis.
abstract: We showed previously that daily gavage of Angelica gigas Nakai (AGN) root ethanolic extract starting 8 weeks of age inhibited growth of prostate epithelium and neuroendocrine carcinomas (NE-Ca) in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Because decursin (D) and its isomer decursinol angelate (DA) are major pyranocoumarins in AGN extract, we tested the hypothesis that D/DA represented active/prodrug compounds against TRAMP carcinogenesis. Three groups of male C57BL/6 TRAMP mice were gavage treated daily with excipient vehicle, AGN (5 mg per mouse), or equimolar D/DA (3 mg per mouse) from 8 weeks to 16 or 28 weeks of age. Measurement of plasma and NE-Ca D, DA, and their common metabolite decursinol indicated similar retention from AGN versus D/DA dosing. The growth of TRAMP dorsolateral prostate (DLP) in AGN- and D/DA-treated mice was inhibited by 66% and 61% at 16 weeks and by 67% and 72% at 28 weeks, respectively. Survival of mice bearing NE-Ca to 28 weeks was improved by AGN, but not by D/DA. Nevertheless, AGN- and D/DA-treated mice had lower NE-Ca burden. Immunohistochemical and mRNA analyses of DLP showed that AGN and D/DA exerted similar inhibition of TRAMP epithelial lesion progression and key cell-cycle genes. Profiling of NE-Ca mRNA showed a greater scope of modulating angiogenesis, epithelial-mesenchymal transition, invasion-metastasis, and inflammation genes by AGN than D/DA. The data therefore support D/DA as probable active/prodrug compounds against TRAMP epithelial lesions, and they cooperate with non-pyranocoumarin compounds to fully express AGN efficacy against NE-Ca.
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas.
authors.forename: Su-Ni
authors.initials: SN
authors.lastname: Tang
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: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas.
authors.forename: Peixin
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Manohar
authors.initials: M
authors.lastname: Puppala
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 Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Chengguo
authors.initials: C
authors.lastname: Xing
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyunghee University, 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. junxuan.lu@ttuhsc.edu.
authors.forename: Junxuan
authors.initials: J
authors.lastname: Lü
mesh_terms: D000230:Adenocarcinoma / Q000517:prevention & control*; D029969:Angelica / Q000737:chemistry*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010936:Plant Extracts / Q000627:therapeutic use*; D018517:Plant Roots / Q000737:chemistry; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D039681:Pyranocoumarins / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D010936:Plant Extracts; D039681:Pyranocoumarins