Ursolic acid inhibits proliferation and stimulates apoptosis in HT29 cells following activation of alkaline sphingomyelinase.
BACKGROUND
Ursolic acid (UA) is a plant component with anti-inflammatory and anti-proliferative properties. Its effect on colon cancer is not clear. We studied the anticancer effects of UA on human colon cancer cells.


METHODS
HT-29 cells were treated with UA. Cell proliferation was determined by cleavage of WST-1. Apoptosis was assayed by cytosolic DNA-histone complex and caspase activity. Sphingomyelinase and alkaline phosphatase were determined against specific substrates.


RESULTS
UA dose-dependently decreased cell proliferation and induced apoptosis, accompanied by activation of caspase 3, 8 and 9. Its antiproliferative effect was stronger than those of sulindac and camptothecin and its apoptotic effect stronger than those of boswellic acid and sulindac. UA selectively increased the activity of intestinal alkaline sphingomyelinase, which occurred before activation of caspases. UA had no effect on alkaline phosphatase activity.


CONCLUSIONS
UA has strong anti-proliferative and apoptotic effects on HT-29 cells. The effects may be mediated by alkaline sphingomyelinase activation.
Andersson
David
D
Gastroenterology Laboratory, Biomedical Centre, B11, Lund University, S-221 84 Lund, Sweden.
Liu
Jian-Jun
JJ
Nilsson
Ake
A
Duan
Rui-Dong
RD
D000469:Alkaline Phosphatase / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
D000469:Alkaline Phosphatase; D000972:Antineoplastic Agents, Phytogenic; D013108:Sphingomyelin Phosphodiesterase; D014315:Triterpenes; D000097245:Ursolic Acid