48-4 |
Milk sphingolipids in prevention of colon cancer and possibly other diseases |
E. M. SCHMELZ, Cancer Institute, Wayne State Univ., 608 OBS, Detroit, MI 48202 Sphingolipids are a structurally diverse class of lipids with a wide range of known functions: they are structural elements in cell membranes, involved in cell-cell, cell-matrix and cell-substratum interactions. Sphingolipid metabolites ceramide, sphingosine and sphingosine-1-phosphate serve as lipid second messengers in the regulation of cell growth, differentiation, and cell death. In the intestinal tract, the same bioactive metabolites are released from dietary complex sphingolipids, and taken up by the intestinal cells. This makes sphingolipids promising candidates for treatment of cancer or other diseases. There are no thorough analyses on sphingolipid content and composition in foods available yet, but milk and milk products are good sources of complex sphingolipids (sphingomyelin, lactosylceramide, glucosylceramide, and ganglioside GD3). These compounds were fed to dimethylhydrazine-treated mice and significantly reduced one of the earliest morphological changes in colon carcinogenesis, aberrant crypt foci. It is still not known if dietary sphingolipids affect colon cancer in humans. However, Min mice (multiple intestinal neoplasia) harbor similar APC mutations found in most patients with familial adenomatous polyposis, and a significant percentage of sporadic tumors. A mixture of sphingolipids (as they appear in milk) at 0.1% of the diet significantly reduced the number of tumors. Adding ceramide to this mixture (while maintaining 0.1% of the diet) reduced the tumor number even further. Immunohistochemical staining of the intestinal sections revealed a relocation of ß-catenin (a protein closely related to tumor formation) to the lateral membranes after feeding sphingolipids; similar effects were seen in vitro in colon cancer cell lines. Therefore, the modulation of ß-catenin may be the first direct mechanistic link between dietary sphingolipids and the suppression of colon carcinogenesis.
Session 48, Dairy foods: More than just good nutrition
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