Trigonella foenum graecum (fenugreek) is traditionally used to treat disorders such as high cholesterol, diabetes, wounds, inflammation, and gastrointestinal ailments. Recently we have shown that diosgenin a major constituent of fenugreek inhibit human colon cancer cell growth and induce apoptosis and suppress the carcinogen-induced colonic aberrant crypt foci in rats (CEBP, 13: 1-7, 2004). However, there are no studies indicating disogenin indeed inhibits carcinoma formation in established animal models of colon cancer. The present double-blind study was designed to assess the potential chemopreventive properties of diosgenin on azoxymethane (AOM)-induced rat colon carcinogenesis. Colonic adenocarcinomas were chosen as chemopreventive efficacy end point. In addition, we assessed the markers of proliferation and apoptosis in colonic tumors and normal appearing crypt to understand the mechanism of tumor growth inhibition of diosgenin. Male F344 rats at 7-weeks of age were fed the control (AIN-76A diet) and one week later, rats received s.c. injections of AOM (15 mg/kg body wt., once weekly for 2 weeks) or equal volume of normal saline (vehicle). One week after the carcinogen treatment groups of rats fed experimental diets containing 0 or 0.1% of diosgenin and continued on the experimental diets for 48 weeks and sacrificed. Colon tumors were evaluated histopathologically and expression levels of markers associated with proliferation and apoptosis were determined in colon tumors and normal appearing colon. Administration of diosgenin significantly suppressed both invasive and non-invasive colon tumor incidence up to 60% (p<0.0004). Similarly, colon tumor multiplicity (adenocarcinomas/rat) significantly suppressed (∼68%, p<0.0001) in rats fed diosgenin diet. In colonic crypts and tumors of animals fed diosgenin there was a significant increase in BrdU labeling (p<0.005) and decrease in PCNA labeling (p<0.001) when compared to animals fed the control diet. The results of this study for the first time provide strong evidence that diosgenin, a naturally-occurring steroidal saponin of fenugreek, possess strong chemopreventive activity against colon carcinogenesis. These results pave the way further development of diosgenin for human clinical trials (Supported by R01 CA-80003 and R01 CA-94962 from the National Cancer Institute).

[Proc Amer Assoc Cancer Res, Volume 46, 2005]