Chemoprevention of azoxymethane/dextran sodium sulfate-induced colon
carcinogenesis in mice by yams and its constituent diosgenin
Noriyuki Miyoshi2, Tomoki Nagasawa2, Hiroshi Noguchi1,3, Takuji Tanaka4,5,
Keiji Wakabayashi2, and Hiroshi Ohshima1,2,1
Global COE Program, 2Graduate School of Nutritional and Environmental Sciences,3
Graduate School of Pharmaceutical Sciences, University of Shizuoka, 4Tokai Cytopathology
Institute, 5Department of Oncologic Pathology, Kanazawa Medical University

Colorectal cancer is one of the most common cancers worldwide and prevalent causes ofmorbidity and mortality. Epidemiological studies have shown that Western-style diet (high in fat andcalories and low in fiber and complex carbohydrates) is associated with an increase risk of colorectal
cancer, indicating that diet would be the most important exogenous life-style related factor in the
etiology of colorectal cancer. It has been estimated that 70% of colorectal cancers could be prevented
by nutritional intervention. Moreover recent studies have shown that obesity and related metabolic
abnormalities, including hyperglycemia and hyperlipidemia, are associated with an increase risk ofcolorectal cancer. Yams (dioscorea) are perennial trailing rhizome plants of the Dioscorea genus(belong to the Dioscoraceae family). The tuber of yam is rich in many nutrients and is consumed as afood in Africa, Asia, Latin America and Oceania. Diosgenin is an aglycone of the steroidal saponin,
dioscin, which is present at relatively high concentrations in the tuber of yams and seed of fenugreek.
The health benefits of diosgenin have so far been shown in preclinical studies and include its efficacy
against hyperglycemia, and hyperlipidemia. It is also reported that diosgenin showedanti-inflammatory and anti-proliferative activities in various cancer cell lines.
In this study, we investigated the effects of diosgenin and several species of freeze-dried yams on
the colon carcinogenesis initiated with a single i.p. injection of azoxymethane (AOM; 10 mg/kg bw)
and promoted by administration of 1.5% dextran sodium sulfate (DSS) in drinking water for 7 days inmale ICR mice. Diosgenin, sanyaku (a traditional chinese medicine, freeze-dried Chinease yam),freeze-dried samples of yamato-imo (Yamato yam), naga-imo (Long yam) and jinenjo (Japanese yam)were given in the diet (20, 100 or 500 mg/kg) to AOM/DSS-treated mice for 17 weeks. Pathologicalexaminations showed that diosgenin and sanyaku significantly suppressed the AOM/DSS-inducedcolon cancer at all doses, but other yams were less effective. GC-MS analyses revealed that diosgenin
was contained in sanyaku (0.0064% wt/wt) but not in other yams. These results suggest that diosgenin
may be a possible chemopreventive agent present in yam. Microarray and quantitative RT-PCRanalyses revealed that diosgenin administration altered expressions of hepatic genes associated withlipid metabolism. In particular the expression of lipoprotein lipase was 12-fold increased by diosgenin
and could contribute to lowering the serum triglyceride levels. Our results imply that diosgenin and“sanyaku” could be used as a potent chemopreventive agent against colon carcinogenesis in humans.