title: Daikenchuto (TU-100) Suppresses Tumor Development in the Azoxymethane and APCmin/+Mouse Models of Experimental Colon Cancer.
abstract: Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APCmin/+mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and β-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA.|Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Takumu
authors.initials: T
authors.lastname: Hasebe
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA.|Extra Value Generation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Kanagawa, Japan.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0001-9457-3683
authors.initials: J
authors.lastname: Matsukawa
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA.
authors.forename: Daina
authors.initials: D
authors.lastname: Ringus
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Miyoshi
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hart
authors.affiliation: Tsumura Research Laboratories, Tsumura and Co, Ami, Ibaraki, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Tsumura Research Laboratories, Tsumura and Co, Ami, Ibaraki, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Hokkaido, Japan.|Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Fujiya
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo
authors.affiliation: Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA.
authors.forename: Chong-Zi
authors.initials: CZ
authors.lastname: Wang
authors.affiliation: Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA.
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Bissonnette
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Musch
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA.
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000737:chemistry* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D005894:Panax; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use*; D032106:Zanthoxylum; D030521:Zingiberaceae
chemical_list: D010936:Plant Extracts; C121414:dai-kenchu-to; D001397:Azoxymethane
keywords: EGF receptor; Kampo; adenomatous polyposis coli; ginseng; β-catenin