Author(s): Sunagawa N, Inamine M, Morioka T, Chiba I, Morita N,
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Abstract The aim of the present study was to examine whether crude glycosphingolipid (cGSL) has short-term chemopreventive effects on the preneoplastic biomarker lesions involved in carcinogen-induced rat colon carcinogenesis. We also examined whether cGSL affects cell proliferation and apoptosis in these lesions. The crude preparation was obtained by the simple ethanol extraction method. Five-week-old male F344 rats were divided into 6 groups. Rats in groups 1-4 were given subcutaneous injections of azoxymethane (AOM) (20 mg/kg body weight) once a week for 2 weeks. Starting 1 week before the first injection of AOM, the rats in groups 2, 3 and 4 were fed a diet containing 250, 1,000 and 3,000 ppm cGSL, respectively, for 5 weeks. The experiment was terminated 5 weeks after the start date, and the number of aberrant crypt foci (ACF) and mucin-depleted foci (MDF) was counted. Dietary cGSL significantly inhibited the induction of ACF (group 3, P<0.01; group 4, P<0.05) and MDF (groups 2 and 3, P<0.001; group 4, P<0.05) as compared to group 1 treated with AOM alone. In groups 3 and 4, proliferating cell nuclear antigen-positive indices of epithelial cells were significantly lower than in group 1 (group 3, P<0.05; group 4, P<0.005). Caspase-3-positive indices were significantly higher in groups 3 and 4 than in group 1 (group 3, P<0.01; group 4, P<0.001). These results suggest that dietary cGSL had a potent chemopreventive effect in the present short-term colon carcinogenesis bioassays, and that this effect may be associated with the inhibition of ACF and MDF and the induction of apoptosis.
This article was published in Mol Med Rep
and referenced in Journal of Addiction Research & Therapy