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

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• 作者：Takumu Hasebe ; Jun Matsukawa ; Daina Ringus ; Jun Miyoshi ; John Hart ; Atsushi Kaneko ; Masahiro Yamamoto ; Toru Kono ; Mikihiro Fujiya ; Yutaka Kohgo ; Chong-Zi Wang ; Chun-Su Yuan ; Marc Bissonnette ; Mark W. Musch and Eugene B. Chang
• 刊名：Phytotherapy Research
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：31
• 期：1
• 页码：90-99
• 全文大小：1314K
• ISSN：1099-1573

文摘

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^min/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APC^min/+ 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