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

• Published in: Phytotherapy research 2017-01, Vol.31 (1), p.90-99
• Main Authors: Hasebe, Takumu, Matsukawa, Jun, Ringus, Daina, Miyoshi, Jun, Hart, John, Kaneko, Atsushi, Yamamoto, Masahiro, Kono, Toru, Fujiya, Mikihiro, Kohgo, Yutaka, Wang, Chong-Zi, Yuan, Chun-Su, Bissonnette, Marc, Musch, Mark W, Chang, Eugene B
• Format: Article
• Language: English
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.5735

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 APC super(min/+) mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30weeks. APC super(min/+) mice were fed diet without or with TU-100 starting at 6weeks, and sacrificed at 24weeks. In both models, dietary TU-100 decreased tumor size. In APC super(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 beta -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.