Trigonella foenum graecum (fenugreek) is traditionally used to treat various health disorders including diabetes, high cholesterol, wounds, inflammation, and gastrointestinal ailments. Recent studies suggest that fenugreek and its active constituents may possess anticarcinogenic potential. We evaluated the preventive efficacy of dietary fenugreek seed and its major steroid saponin constituent diosgenin on azoxymethane (AOM) -induced rat colon carcinogenesis during initiation and promotional stages. Colonic preneoplastic lesions or aberrant crypt foci (ACF) were chosen as end-points. In addition, we assessed the preventive mechanisms of diosgenin in the HT-29 human colon cancer cell line. To evaluate the effect during the initiation and postinitiation stages, 7-week-old male F344 rats were fed experimental diets containing 0, 1% fenugreek seed powder (FSP), or 0.05% or 0.1% diosgenin continuously and were then injected with AOM a week later; effects during the promotional stage was studied by feeding 1% FSP and 0.1% diosgenin 4-weeks after AOM-injections. Rats were sacrificed 8-weeks after AOM-injection and their colons were either evaluated for aberrant crypt foci (ACF) or for molecular markers. Dietary 1% FSP, 0.05% and 0.1% diosgenin administered continuously suppressed total colonic ACF up to 32%, 24% and 42% (p ≤ 0.001-0.0001), respectively. Dietary 1% FSP and 0.1% diosgenin fed only during the promotional stage also inhibited total ACF up to 33% (p ≤ 0.001) and 39% (p ≤ 0.0001), respectively. Importantly, upon continuous feeding of 1% FSP, 0.05% or 0.1% diosgenin the numbers of colonic ACF with multiplicity ≥ 4 were 38%, 20% and 36% lower than in controls (p ≤ 0.001). Feeding 1% FSP or 0.1% diosgenin resulted in 25% and 32% lower (p ≤ 0.001) incidence of multi-crypt ACF than in controls. Dietary diosgenin inhibited total colonic ACF and multi-crypt ACF formation in a dose-dependent manner. Diosgenin also inhibited proliferation and induced apoptosis in the HT-29 human colon cancer cell lines in a dose-dependent manner. Our results suggest that diosgenin induced apoptosis in HT-29 cells at least in part through modification of bcl-2 and caspase-3 levels. These findings add new insights into the development of fenugreek seeds and/or diosgenin as possible colon cancer-preventive agents. {Supported by NCI Grant CA-80003}

[Proc Amer Assoc Cancer Res, Volume 45, 2004]