Sphingomyelin in the suppression of colon tumors: prevention versus intervention.
Intestinal cells are regularly exposed to sphingolipid metabolites, i.e., ceramide and sphingoid bases, after hydrolysis of complex sphingolipids from the diet. These metabolites are known regulators of cell growth, differentiation, and death. Non-pharmacological amounts in the diet have been shown to inhibit early stages of chemically induced colon cancer in mice. To distinguish between chemopreventive and chemotherapeutic effects of sphingomyelin supplements, mice were fed sphingomyelin before and after tumor initiation. Both applications drastically reduced tumor formation, without a significant difference among the groups, indicating that sphingolipids are as effective in the chemoprevention of tumors as in early intervention. The normalization of cell proliferation and rate of apoptosis, but not the induction of differentiation, seem to be key players in the suppression of tumor formation by dietary sphingomyelin. This may have implications for the development of a cancer prevention or treatment strategy with sphingolipids as an alternative to conventional drugs.
Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Lori A
LA
Lemonnier
Dirck L
DL
Dillehay
Michael J
MJ
Vespremi
Judith
J
Abrams
Ernest
E
Brody
Eva M
EM
Schmelz
D019813:1,2-Dimethylhydrazine; D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D051379:Mice; D011230:Precancerous Conditions / Q000517:prevention & control*; D013109:Sphingomyelins / Q000008:administration & dosage*
D002791:Cholesterol, Dietary; D013109:Sphingomyelins; D019813:1,2-Dimethylhydrazine