Inhibitory effect of dietary monoglucosylceramide 1‐O‐β‐glucosyl‐N‐2′‐hydroxyarachidoyl‐4,8‐sphingadienine on two different categories of colon preneoplastic lesions induced by 1,2‐dimethylhydrazine in F344 rats

Abstract

Sphingolipids display a wide spectrum of biological activities, including cell growth, differentiation and apoptosis. However, precise mechanisms by which these compounds exert anticancer or cancer-preventive effects are not known. In the present study, we evaluated the preventive efficacy of enriched dietary monoglucosylceramide 1-O-β β β β-glucosyl-N-2′ ′ ′ ′-hydroxyarachidoyl-4,8-sphingadienine (G 1 CM) on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) and β β β β-catenin-accumulated crypt (BCAC) formation in F344 rats during initiation stage. We also examined whether G 1 CM affects cell proliferation and apoptosis in these lesions. Pure G 1 CM was isolated from rice bran. Forty-two rats were divided randomly into five experimental groups. Rats in groups 1-3 were given subcutaneous injections of DMH (40 mg/kg body weight) once a week for 2 weeks. One week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 200 and 1000 p.p.m. G 1 CM, respectively, for 5 weeks. Rats in group 4 were fed a diet containing 1000 p.p.m. G 1 CM. Rats in group 5 were given the basal diet alone and served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary G 1 CM at both doses (groups 2 and 3) significantly inhibited the induction of ACF and BCAC (P < 0.001) when compared to group 1 treated with DMH alone. In groups 2 and 3, the proliferating cell nuclear antigen labeling indices of epithelial cells in ACF and BCAC were also lower than in group 1 (P < 0.0001 for ACF, P < 0.05 for BCAC).

The potential of sphingomyelin as a chemopreventive agent in AOM‐induced colon cancer model: wild‐type and p53+/– mice

“…Our previous studies have shown that defective AARGC is associated with increased risk for CRC in p53 +/ -and p53 -/ -mice [28,29], and that up-regulation of AARGC by a variety of dietary agents and drugs is associated with protection for CRC [29, 35, 48 -52]. In keeping with earlier studies [5,34,47], our study showed that SM intake (0.05 -0.1%) did not affect baseline apoptosis. Furthermore, it did not increase AARGC or apoptosis in tumours nor did it restore defective AARGC characteristic of p53 +/ -mice.…”

“…Lemonnier et al [34] showed that dietary intake of SM normalized apoptosis, but not beyond the level of control group. Other studies have shown no difference between the number of apoptotic cells in the colonic epithelium of control and SM diet [5,34,47]. With respect to the potential of dietary SM on preventing tumour initiation, our particular interest was to examine whether SM regulated the apoptotic response to DNA damage (AARGC), which is important for eliminating DNA-damaged cells during tumour initiation [35].…”

By-products of Rice Processing: An Overview of Health Benefits and Applications

“…Rice bran inhibits the growth of human colon cancer cells [85], and rice bran consumption reduces the number of intestinal adenomas in APC Min mice, an animal model of human familial adenomatous polyposis (FAP) [86]. Finally, DMH-and AOM-induced preneoplastic lesions are inhibited by rice bran-derived sphingolipids in the colons of rats [87,88].…”

Chemical Analysis of the Sugar Moiety of Monohexosylceramide Contained in Koji, Japanese Traditional Rice Fermented with Aspergillus

“…For example, the dietary intake of glucosylceramide prevents colon preneoplastic lesions [15] and head and neck cancers [16,17]. Also, when administered to the skin, it improves skin disorders [18].…”