出版社:American Society for Biochemistry and Molecular Biology
摘要:Butyric acid and sphingomyelin (SM) affect colonic tumorigenesis.We examined the potential link between butyrate stimulationand SM metabolism in colonic and hepatic cancer cell lines.After incubating HT29 and HepG2 cells with butyrate and othershort-chain fatty acids, we found that butyrate increased acidbut not neutral or alkaline sphingomyelinase (SMase) activityby 10- to 20-fold. The effects occurred after 16 h of incubationand were associated with reduced SM and phosphatidylcholinecontents and increased ceramide levels. Northern blotting showedincreased acid SMase mRNA levels in these cells after butyratestimulation. Propionate was less potent, and acetate had noeffect. No similar changes of acid phosphatase could be identified.At concentrations that increased acid SMase expression, butyrateinhibited cell proliferation, activated caspase 3, and inducedapoptosis. However, the antiproliferative and apoptotic effectsof butyrate preceded the changes of acid SMase and were notaffected by knocking down acid SMase expression by small, interferingRNA. In addition, butyrate-induced acid SMase expression wasnot affected by blocking the caspase pathway.
In conclusion, butyrate regulates SM metabolism by stimulatingacid SMase expression in colon and liver cancer cells, but theincreased acid SMase is not a critical mechanism for initiatingthe anticancer effects of butyrate.Supplementary key words short-chain fatty acid • colon • liver • sphingomyelin • apoptosis • caspase • small, interfering RNA