Carnosol inhibits β-catenin tyrosine phosphorylation and prevents adenoma formation in the C57BL/6J/Min/+ (Min/+) mouse

Amy E. Moran, Adelaide M. Carothers, Michael J. Weyant, Mark Redston, Monica M. Bertagnolli

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1097-1104
Number of pages8
JournalCancer Research
Volume65
Issue number3
StatePublished - Feb 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Moran, A. E., Carothers, A. M., Weyant, M. J., Redston, M., & Bertagnolli, M. M. (2005). Carnosol inhibits β-catenin tyrosine phosphorylation and prevents adenoma formation in the C57BL/6J/Min/+ (Min/+) mouse. Cancer Research, 65(3), 1097-1104.