RRC ID 73717
Author Momen MA, Monden Y, Houchi H, Umemoto A.
Title Effect of ursodeoxycholic acid on azoxymethane-induced aberrant crypt foci formation in rat colon: in vitro potential role of intracellular Ca2+.
Journal J Med Invest
Abstract The studies were conducted to examine the precise nature of the suppressive effect of ursodeoxycholic acid (UDCA) on colonic aberrant crypt foci (ACF) formation. Fischer 344 rats were treated with a single dose of azoxymethane (AOM) (20 mg/kg, s.c.) and fed basal diet (MF) supplemented with UDCA (0.4%) during an initiation or a post-initiation stage. ACF were enumerated at the 2nd, 5th and 8th weeks after AOM administration (15-18 rats/group). The number of ACF in the UDCA treated group was decreased significantly in the initiation and post-initiation stages at the 2nd (P < 0.01, P < 0.0001) and 8th weeks (P < 0.001, P < 0.0001), respectively, compared with untreated controls. In the time-course experiments, the effect of continuous feeding of UDCA (0.4%) on ACF formation was evaluated. ACF number was decreased significantly (P < 0.005) until the 16th week. UDCA showed a significant dose-dependent suppression of ACF number from a range of 0.1-0.4% UDCA. To approach the subcellular mechanisms of the effect of bile acids, the intracellular free Ca2+ concentration ([Ca2+]i) of bile acid-treated rat colonic cancer cells (ACL-15) was examined. DCA and CDCA, which are promotive on ACF formation, induced a rapid increase in [Ca2+]i, while UDCA and CA, which are suppressive or non-effective on ACF formation, did not. These findings suggest that the promotive effect of bile acids may involve intracellular Ca2+ signaling.
Volume 49(1-2)
Pages 67-73
Published 2002-2-1
PMID 11901763
MeSH Animals Anticarcinogenic Agents / pharmacology* Azoxymethane / antagonists & inhibitors* Azoxymethane / toxicity* Bile Acids and Salts / pharmacology Calcium / metabolism Calcium / physiology* Calcium Signaling / drug effects Calcium Signaling / physiology Carcinogens / adverse effects Carcinogens / antagonists & inhibitors* Colon / drug effects Colon / pathology* Colonic Neoplasms / pathology Colonic Neoplasms / prevention & control Diet Disease Models, Animal Dose-Response Relationship, Drug Intracellular Fluid / metabolism* Male Rats Rats, Inbred F344 Tumor Cells, Cultured Ursodeoxycholic Acid / pharmacology*
Human and Animal Cells ACL-15(RCB0510)