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. MATERIALS AND 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. CONCLUSION: UA has strong anti-proliferative and apoptotic effects on HT-29 cells. The effects may be mediated by alkaline sphingomyelinase activation.