Curcumin decreases acid sphingomyelinase activity in colon cancer Caco-2 cells.
Curcumin has been shown to inhibit cell growth and induce apoptosis in colon cancer cells. The metabolism of sphingomyelin has implications in the development of colon cancert. We examined whether curcumin affects the enzymes that hydrolyse sphingomyelin in Caco-2 cells. The cells were cultured in both monolayer and polarized conditions and stimulated with curcumin. The activities of sphingomyelinases were determined. Sphingomyelin and its hydrolytic products were analysed by thin layer chromatography. The changes of acid sphingomyelinase protein were examined by Western blotting. We found that curcumin reduced the hydrolytic capacity of the cells against choline-labelled sphingomyelin, associated with a mild increase of cellular sphingomyelin in the cells. Analysis of the hydrolytic products revealed that the activity was derived from acid sphingomyelinase not from phospholipase D. The curcumin-induced reduction of acid SMase required more than 8 h stimulation. Western blotting showed reduced acid sphingomyelinase protein after curcumin stimulation. The inhibitory effect was more potent in monolayer cells than in polarised cells. No changes of other sphingomyelinases were identified. In the concentrations inhibiting acid sphingomyelinase, curcumin inhibited DNA synthesis and induced cell death. In conclusion, curcumin inhibits acid sphingomyelinase and the effect might be involved in its antiproliferative property against colon cancer cells.
Cheng
Yajun
Y
Biomedical Centre, B11, Institution of Clinical Sciences, Lund University, Lund, Sweden.
Kozubek
Agnieszka
A
Ohlsson
Lena
L
Sternby
Berit
B
Duan
Rui-Dong
RD
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells / Q000187:drug effects / Q000201:enzymology; D049109:Cell Proliferation / Q000187:drug effects; D030024:Curcuma; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013108:Sphingomyelin Phosphodiesterase / Q000187:drug effects* / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D013108:Sphingomyelin Phosphodiesterase; D003474:Curcumin