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Nutrition and Cancer

Adenoma Growth Stimulation by the trans-10, cis-12 Isomer of Conjugated Linoleic Acid (CLA) Is Associated with Changes in Mucosal NF-B and Cyclin D1 Protein Levels in the Min Mouse

Johanna Rajakangas³, Samar Basu^*, Irma Salminen and Marja Mutanen

Department of Applied Chemistry and Microbiology, Division of Nutrition, University of Helsinki, Helsinki, Finland; ^* Section of Geriatrics and Clinical Nutrition Research, Faculty of Medicine, Uppsala University, Uppsala, Sweden; and Department of Nutrition, National Public Health Institute, Helsinki, Finland

³To whom correspondence should be addressed. E-mail: johanna.rajakangas{at}helsinki.fi.

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)F₂. 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)-B 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 ß-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-B and cyclin D1.

KEY WORDS: • Min mouse • conjugated linoleic acid • colon cancer

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