Dietary lipids modulatory effects on colon cancer cells

Dietary lipids, especially specific fatty acids are important modulators of various physiological functions and significantly contribute to maintenance of intestinal epithelium homeostasis. Disturbance of this homeostasis substantially contribute to colon cancer development. We investigated and compared the response of human epithelial cell lines derived from fetal colon (FHC) and colon adenocarcinoma (HT-29) to i) docosahexaenoic acid (DHA), an essential ω-3 polyunsaturated fatty acid, ii) sodium butyrate (NaBt), short chain fatty acid produced by microbial fermentation of fibre in the colon, and iii) their combination. We supposed mutual interaction of the signaling pathways triggered by these two fatty acids, which may significantly modulate the cell survival/ death.

Using fluorimetry, flow cytometry and western blotting methods we investigated various changes in cytokinetic and lipid metabolism parameters. Our results showed that NaBt alone or in combination with DHA can decrease proliferation (CyQUAN T, cell cycle analysis), induce differentiation (alkaline phosphatase activity), apoptosis (caspase-3 and PAR P cleavage) and also autophagy (LC3 cleavage) depending on cell line and time of treatment. These effects were associated with alteration in lipid droplet accumulation, reactive oxygen species production, mitochondrial membrane potential and with modulation of the expression or activity of some regulatory molecules connected with lipid metabolism such as fatty acid synthase, caveolin-1 and peroxisome proliferator-activated receptor (PPAR ) γ.

These results point out the important role of dietary lipids in colon epithelial cell behaviour. Supported by grants Nos. P301/11/1730 and 13–09766S of Czech Science Foundation.