Dietary Sphingomyelin Inhibits Colonic Tumorigenesis with an Up-regulation of Alkaline Sphingomyelinase Expression in ICR Mice

Abstract

Background: Sphingomyelin (SM) hydrolysis generates biologically active products regulating cell growth, differentiation and apoptosis. Dietary SM has been found to inhibit colonic tumorigenesis. Alkaline sphingomyelinase (alk-SMase) is the key enzyme responsible for sphingomyelin digestion in the gut. Whether or not dietary sphingomyelin affects alk-SMase expression was examined in a colon cancer animal model. Materials and Methods: Imprinting control region (ICR) mice were injected with 1,2-dimethylhydrazine (DMH) and then fed a diet with or without SM (0.5g/kg in diet) for 22 weeks. The colonic tumorigenesis and alk-SMase activity were determined and alk-SMase expression was examined by Western blot and PCR. Results: Dietary SM inhibited the tumorigenesis and increased the alk-SMase activity in the colon by 65% . The increased activity was associated with increased enzyme protein and mRNA expression. No changes of acid and neutral sphingomyelinase activities were found. Conclusion: Long-term supplementation with dietary sphingomyelin up-regulates colonic alk-SMase expression, which may contribute to the inhibitory effects of sphingomyelin against colonic carcinogenesis.