BACKGROUND. Conjugated linoleic acids (CLAs) have anti-tumorigenic properties in animal models and anti-proliferative effects on cancer cells in vitro. Previous studies have shown that the NF-kappa B pathway is involved regulating anti-apoptotic gene expression. The present study investigated the effects of CLAs (cis-9, trans-11, and trans-10, cis-12 isomers and a 50:50 mixture) on apoptosis and NF-kappa B activation in LNCaP cells.
METHODS. Apoptosis was assessed by annexin V staining using flow cytometry. TNF-alpha-induced NF-kappa B activity was determined by gel shift and reporter gene assays in addition to monitoring I kappa B alpha phosphorylation.
RESULTS. Only the CLA cis-9, trans-11 isomer significantly increased TNF-alpha-induced apoptosis (by 59%), which correlated with a reduction in NF-kappa B transcriptional activity (by 35%, P < 0.05), NF-kappa B binding activity (by 15%, P < 0.05), and phosphorylation of I kappa B alpha (by 36%, P < 0.01).
CONCLUSIONS. Our results may offer a mechanistic explanation for the reported inhibition of prostate tumor growth by CLAs in animal models of disease.
- conjugated linoleic acids
- NF-kappa B
- I kappa B phosphorylation
- prostate cancer cells
- mammary carcinogenesis