Biological effects of conjugated linoleic acid: analysis, enrichment and mode of cytotoxicity in cancer cell lines
O'Shea, Marianne (2000) Biological effects of conjugated linoleic acid: analysis, enrichment and mode of cytotoxicity in cancer cell lines. PhD thesis, Dublin City University.
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Conjugated linoleic acid (CLA) refers to a class of conjugated dienoic isomers of linoleic acid produced by ruminant animals. The predominant dietary sources o f CLA (cis-9, trans-11) are ruminant fat products such as milk, beef and dairy products. CLA has been shown to be anti-carcinogenic, anti-atherosclerotic, and anti-catabolic. In this study methodology for analysis of trans fatty acids (TFA) was optimised using a combination of silver-ion chromatography and GLC, and applied to the analysis of CLA and TFA in a range of Irish dairy products. Having established levels of CLA in Irish dairy products, fractionation of anhydrous milk fat was investigated as a means of enriching the levels of this fatty acid within a food ingredient. Dry fractionation with a temperature range between 33-10 °C and a cooling rate of 0.54 °C/h, led to a soft fraction enriched in polyunsaturates and low in saturates with a CLA content that was 60.3 % elevated compared with the starting material. Its anticarcinogenic effect was demonstrated in mammary and colon cancer cell lines. A synthetic CLA mixture inhibited the growth of mammary MCF-7 and colon SW480 cancer cells in a dose and time dependent manner. Superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and thiobarbituric reactive substances (TBARS) were induced in both cell lines exposed to CLA (20ppm) over a period o f 12 days. Similar effects were observed in MCF-7 cells treated with the pure c9, t 11 CLA isomer and with bovine milk fat from animals fed pasture, rapeseed or soya. Growth suppression o f these cells was independent of the source of CLA. Equimolar concentrations of linoleic acid (LA) promoted the growth of the MCF-7 cell line. CLA and LA exerted differential effects on protein famesyl transferase (PFTase) activity, the rate limiting enzyme in famesylation of ras oncoproteins in cancer cells, thus implicating modulation of PFTase activity in CLA-mediated growth suppression. Multiple biochemical mechanisms appear to be involved in the growth suppressive effects of CLA isomers in vitro.
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