Informace o publikaci
Response of normal vs. cancer colon cells to short- and long-chain fatty acids
| Autoři | |
|---|---|
| Rok publikování | 2008 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Dynamic balance between proliferation, differentiation and apoptosis is necessary for healthy intestinal epithelium. Together with endogenous regulators dietary lipid compounds like esential polyunsaturated fatty acids (PUFAs) and short chain fatty acid – butyrate (produced by microbial fermentation of fibre) can play an important role in maintaining homeostasis in this tissue. Signals induced by these factors are integrated inside the cells and may have significant impact on cell metabolism and kinetics. Processes of colon cell differentiation and apoptosis are accompanied with changes of biophysical properties of cell membranes, and by modulation of constitution, structure, symmetry and metabolism of cell lipids. Suggesting differences of these events in normal and tumor cells we compared the response of human colonic cell lines derived from normal fetal tissue (FHC) and colon adenocarcinoma (HT-29, HCT116) to treatment with sodium butyrate (NaBt, 3 mM) and PUFAs (50 microM) of n-6 (arachidonic acid, AA) or n-3 (docosahexaenoic acid, DHA) series and their combination. Using flow cytometry as the main methodology we detected modulations of proliferation, differentiation (activity of alkaline phosphatase), and cell death (% of floating cells, nuclear morphology). FHC cells were more sensitive to NaBt, PUFAs and especially to theircombination than cancer cells. Induction of FHC cell apoptosis was associated with decrease omitochondrial membrane potential (MMP- TMRE), membrane lipid unpacking (MC540), acumulation of lipid droplets (NILE RED). The role of oxidative stress (detection of ROS, DHR-123) and caspases was verified by using appropriate antioxidants (NAC, TROLOX) and caspase inhibitor Z-VAD. Content and composition of phospholipids and fatty acids (LC/MS, GC/MS) after treatment of agents studied differed in normal and cancer cells. Detection of these alterations and their correlation with other parameters reflecting differentiation and apoptosis contribute to clarifying of sequencing and regulation of particular steps of these processes and differences between normal and cancer cells. This work was supported by grants No. 524/07/1178 GACR, 301/07/1557 GACR, 1QS500040507 IGA ASCR |