Ursodeoxycholic Acid Increases the Activities of Alkaline Sphingomyelinase and Caspase-3 in the Rat Colon

Abstract

Background: Ursodeoxycholic acid (UDCA) has been found to inhibit the development of colon carcinoma induced by chemical carcinogens with unidentified mechanisms. Sphingomyelin metabolism has emerged as a novel signal transduction pathway closely related to cell proliferation and apoptosis. We recently found that alkaline sphingomyelinase (SMase) activity was decreased in human colon cancer. The present study is to investigate whether UDCA has effect on the levels of SMase and whether the activity of caspase-3, a key regulatory protease in apoptosis that can be activated by sphingomyelin breakdown products, is also influenced by UDCA. Methods: Rats were fed UDCA in amounts ranging from 37.5 to 300 mg/kg/day for 10 days by gavage. The colonic mucosa was scraped, homogenized, and sonicated. The activities of acid, neutral and alkaline SMases, and caspase-3 were determined. Results: UDCA dose-dependently increased alkaline SMase activity in colonic mucosa and faeces, slightly increased acid SMase activity in the mucosa, and had no effect on neutral SMase. UDCA also dose-dependently increased caspase-3 activity in the colonic mucosa, and the increase correlated significantly with the changes in alkaline but not that in acid or neutral SMase activity. Conclusions: UDCA increases alkaline sphingomyelinase and caspase-3 activities, which might be a mechanism involved in its anticarcinogenic effect on colon cancer development.