Adenoma growth stimulation by the trans-10, cis-12 isomer of conjugated linoleic acid (CLA) is associated with changes in mucosal NF-kappaB and cyclin D1 protein levels in the Min mouse.
Conjugated linoleic acid (CLA) is a term used to describe the different conjugated isomers of linoleic acid. CLA has been found to be anticarcinogenic in mammary cancer, but its effects on colon carcinogenesis are still inconclusive. In this study, the isomer-specific effects of the cis-9, trans-11 and trans-10, cis-12 CLA isomers were investigated in the Min mouse model for intestinal carcinogenesis. The Min mice (n = 10/group) were fed either an AIN-93G control diet or a diet containing 1 g/100 g cis-9, trans-11 or trans-10, cis-12 CLA for 8 wk. The number and size of adenomas were measured and the proteins from the small intestinal tissues extracted for immunoblotting analysis. The number of adenomas did not differ, but the size of the adenomas was greater in the distal part of the small intestine in mice fed the trans-10, cis-12 isomer than in controls (1.19 +/- 0.16 vs. 0.94 +/- 0.21 mm, mean +/- SD, P < 0.01). The same isomer caused an increase in lipid peroxidation, measured as urinary 8-iso-prostaglandin (PG)F(2alpha). Nuclear p65 protein of the mucosal tissue was not detectable in the trans-10, cis-12 group, which differed (P < 0.05) from the control group. Cyclin D1, a target for the nuclear factor (NF)-kappaB pathway, was elevated in the trans-10, cis-12 group compared with the control group (P < 0.01), but cyclooxygenase-2 levels were not higher. There was no difference in beta-catenin protein levels between the groups. The results indicate that the trans-10, cis-12 isomer of CLA can act as a cancer promoter in colon carcinogenesis possibly through pathways affecting NF-kappaB and cyclin D1.
Rajakangas
Johanna
J
Department of Applied Chemistry and Microbiology, Division of Nutrition, University of Helsinki, Helsinki, Finland. johanna.rajakangas@helsinki.fi
Basu
Samar
S
Salminen
Irma
I
Mutanen
Marja
M
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D004032:Diet; D007413:Intestinal Mucosa / Q000378:metabolism*; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008041:Linoleic Acids / Q000008:administration & dosage*; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000378:metabolism*; D013237:Stereoisomerism
D008041:Linoleic Acids; D016328:NF-kappa B; D019938:Cyclin D1