Endoscopy 2004; 36 - 22
DOI: 10.1055/s-2004-834510

Chronic but not Acute Treatment with Conjugated Linoleic Acid (CLA) Isomers (CIS-9, Trans-11 CLA and Trans-10, CIS-12 CLA) Inhibit DCA-Induced Protein Kinase C and NF-KB Activation in Humans Colorectal Cancer Cells

SA Shah 1, N Mahmud 1, M Muftah 1, H Roche 1, D Kelleher 1
  • 1Department of Clinical Medicine and Dublin Molecular Medicine Centre, Trinity College and St James's Hospital Dublin

Background: High dietary fat is known to increase the risk of colorectal cancer in while conjugated linoleic acids (CLA) are reported to inhibit cancer growth. Deoxycholic acid (DCA) is known to activate protein kinase C (PKC) isoenzymes and NF-κB. The aim of study was to examine the effects of CLA on DCA-induced PKC and NF-κB signalling in colon cancer.

Materials and Methods: HCT 116, treated with CLA isomers (cis-9, trans-11 CLA, trans-10, cis-12 CLA) for 24 hours or 14 days, were transfected with PKC β 1-EGFP (enhanced green fluorescent protein), PKC δ -EGFP or PKC ζ -EGFP. Cells were activated with DCA or C2-Ceramide. PKC translocation was observed using real time photomicroscopy and fluorescent microscopy. Gel shift assays were performed on nuclear extracts of cells for NF-κB analyses.

Results: Chronic (14 days) treatment of cells with 50 ì M cis-9, trans-10 CLA, inhibited DCA-induced PKC β 1, PKC δ and C2-Cramide-induced of PKC ζ translocation. CLA isomers also inhibited DCA and IL-1 β-induced activation of NF-κB.

Conclusion: In conclusion this study indicates that CLA inhibit PKC and NF-κB activation in colon cancer cells. These data provide suggestive evidence for mechanisms whereby CLA in diet might influence the course of colonic cancer.