Dietary sphingomyelin inhibits colonic tumorigenesis with an up-regulation of alkaline sphingomyelinase expression in ICR mice.
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.


METHODS
Imprinting control region (ICR) mice were injected with 1,2-dimethylhydrazine (DMH) and then fed a diet with or without SM (0.5 g/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.


CONCLUSIONS
Long-term supplementation with dietary sphingomyelin up-regulates colonic alk-SMase expression, which may contribute to the inhibitory effects of sphingomyelin against colonic carcinogenesis.
Zhang
Ping
P
Department of Hygienic Toxicology, Public Health College, Harbin Medical University, 150081 Harbin, China.
Li
Baixiang
B
Gao
Shuying
S
Duan
Rui-Dong
RD
D019813:1,2-Dimethylhydrazine; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D019587:Dietary Supplements; D005260:Female; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D013108:Sphingomyelin Phosphodiesterase / Q000096:biosynthesis* / Q000235:genetics; D013109:Sphingomyelins / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects
D002273:Carcinogens; D012333:RNA, Messenger; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase; D019813:1,2-Dimethylhydrazine