TY - JOUR
T1 - Carnosol inhibits β-catenin tyrosine phosphorylation and prevents adenoma formation in the C57BL/6J/Min/+ (Min/+) mouse
AU - Moran, Amy E.
AU - Carothers, Adelaide M.
AU - Weyant, Michael J.
AU - Redston, Mark
AU - Bertagnolli, Monica M.
PY - 2005/2/1
Y1 - 2005/2/1
N2 - Carnosol, a constituent of the herb, rosemary, has shown beneficial medicinal and antitumor effects. Using the C57BL/ 6J/Min/+ (Min/+) mouse, a model of colonic tumorigenesis, we found that dietary administration of 0.1% carnosol decreased intestinal tumor multiplicity by 46%. Previous studies showed that tumor formation in the Min/+ mouse was associated with alterations in the adherens junctions, including an increased expression of tyrosine-phosphorylated β-catenin, dissociation of β-catenin from E-cadherin, and strongly reduced amounts of E-cadherin located at lateral plasma membranes of histologically normal enterocytes. Here, we confirm these findings and show that treatment of Min/+ intestinal tissue with carnosol restored both E-cadherin and β-catenin to these enterocyte membranes, yielding a phenotype similar to that of the Apc+/+ wild-type (WT) littermate. Moreover, treatment of WT intestine with the phosphatase inhibitor, pervanadate, removed E-cadherin and β-catenin from the lateral membranes of enterocytes, mimicking the appearance of the Min/+ tissue. Pretreatment of WT tissue with carnosol inhibited the pervanadate-inducible expression of tyrosine-phosphorylated β-catenin. Thus, the ApcMin allele produces adhesion defects that involve up-regulated expression of tyrosine-phosphorylated proteins, including β-catenin. Moreover, these data suggest that carnosol prevents Apc-associated intestinal tumorigenesis, potentially via its ability to enhance E-cadherin-mediated adhesion and suppress β-catenin tyrosine phosphorylation.
AB - Carnosol, a constituent of the herb, rosemary, has shown beneficial medicinal and antitumor effects. Using the C57BL/ 6J/Min/+ (Min/+) mouse, a model of colonic tumorigenesis, we found that dietary administration of 0.1% carnosol decreased intestinal tumor multiplicity by 46%. Previous studies showed that tumor formation in the Min/+ mouse was associated with alterations in the adherens junctions, including an increased expression of tyrosine-phosphorylated β-catenin, dissociation of β-catenin from E-cadherin, and strongly reduced amounts of E-cadherin located at lateral plasma membranes of histologically normal enterocytes. Here, we confirm these findings and show that treatment of Min/+ intestinal tissue with carnosol restored both E-cadherin and β-catenin to these enterocyte membranes, yielding a phenotype similar to that of the Apc+/+ wild-type (WT) littermate. Moreover, treatment of WT intestine with the phosphatase inhibitor, pervanadate, removed E-cadherin and β-catenin from the lateral membranes of enterocytes, mimicking the appearance of the Min/+ tissue. Pretreatment of WT tissue with carnosol inhibited the pervanadate-inducible expression of tyrosine-phosphorylated β-catenin. Thus, the ApcMin allele produces adhesion defects that involve up-regulated expression of tyrosine-phosphorylated proteins, including β-catenin. Moreover, these data suggest that carnosol prevents Apc-associated intestinal tumorigenesis, potentially via its ability to enhance E-cadherin-mediated adhesion and suppress β-catenin tyrosine phosphorylation.
UR - http://www.scopus.com/inward/record.url?scp=13444257363&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13444257363&partnerID=8YFLogxK
M3 - Article
C2 - 15705912
AN - SCOPUS:13444257363
SN - 0008-5472
VL - 65
SP - 1097
EP - 1104
JO - Cancer Research
JF - Cancer Research
IS - 3
ER -