Daikenchuto (TU-100) Suppresses Tumor Development in the Azoxymethane and APCmin/+ Mouse Models of Experimental Colon Cancer

Phytother Res. 2017 Jan;31(1):90-99. doi: 10.1002/ptr.5735. Epub 2016 Oct 12.

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 APC min/+ 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.

Keywords: EGF receptor; Kampo; adenomatous polyposis coli; ginseng; β-catenin.

MeSH terms

  • Animals
  • Azoxymethane / chemistry*
  • Azoxymethane / pharmacology
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Male
  • Medicine, Traditional
  • Mice
  • Panax
  • Plant Extracts / administration & dosage
  • Plant Extracts / therapeutic use*
  • Zanthoxylum
  • Zingiberaceae

Substances

  • Plant Extracts
  • dai-kenchu-to
  • Azoxymethane