Ursolic acid inhibits the formation of aberrant crypt foci and affects colonic sphingomyelin hydrolyzing enzymes in azoxymethane-treated rats

David Andersson, Yajun Cheng, Rui-Dong Duan

Research output: Contribution to journalArticlepeer-review

Abstract

Ursolic acid (UA) is a pentacyclic triterpenoid, with anti-cancer and anti-inflammatory properties. Sphingomyelin (SM) hydrolysis generates lipid messengers regulating cell survival. Earlier studies showed that UA has anti-proliferative and apoptotic effects on HT29 cells, accompanied by a rapid increase in alkaline sphingomyelinase (Alk-SMase) activity. This study examines the effect of orally administered UA on the formation of aberrant crypt foci (ACF) and intestinal SMase activity in azoxymethane (AOM)-treated rats. Sprague-Dawley rats were divided into eight groups, receiving AOM or vehicle, and fed normal diet or pellets containing 0.11% UA in the initiation or promotion/progression phase. The formation of ACF in the colon and the activities of three types of mucosal SMase were examined. UA significantly reduced the incidence of ACF containing three or more crypts in the initiation group, but had no significant effect in the promotion/progression group. AOM reduced mucosal Alk-SMase activity, and the inhibitory effects could not be prevented by UA. However, in both AOM-treated and normal rats, UA increased the activity of colonic neutral SMase markedly and that of acid SMase activity mildly. These results indicate that UA has chemopreventive effects in the initiation phase of colon cancer associated with changes in SM metabolism.
Original languageEnglish
Pages (from-to)101-107
JournalJournal of Cancer Research and Clinical Oncology
Volume134
Issue number1
DOIs
Publication statusPublished - 2008

Subject classification (UKÄ)

  • Cancer and Oncology

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