Eicosapentaenoic acid and docosahexaenoic acid effects on tumour mitochondrial metabolism, acyl CoA metabolism and cell proliferation

In order to investigate the effects of high-fat diets rich in eicosapentaen oic acid (EPA) and docosahexaenoic acid (DHA), Wistar rats bearing subcutan eous implants of the Walker 256 tumour were fed pelleted chow containing lo w DHA/EPA or high DHA/EPA. The presence of n-3 polyunsaturated fatty acids (PUFAs) led to a marked suppression (35-46%) of tumour growth over a 12 day period. Both the whole tumour homogenate and the Percoll-purified mitochon drial fraction presented significant changes in fatty acid composition. The levels of EPA increased in both n-3 dietary groups while the levels of DHA increased only in the high DHA/EPA group, in comparison with the control c how-fed group. The presence of n-3 PUFAs led to an increase in mitochondria l acyl CoA synthetase activity, but neither the cytoplasmic acyl CoA conten t nor the n-3 fatty acid composition of the cytoplasmic acyl CoAs was alter ed by the diet. The content of thiobarbituric acid-reactive substances (TBA RS) was increased in the low DHA/EPA group but was unchanged in the high DH A/EPA group. In vitro studies with the Walker 256 cell line showed a 46% de crease in cell growth in the presence of either EPA or DHA which was accomp anied by a large decrease in the measured mitochondrial membrane potential. The TBARS content was increased only in the EPA-exposed cells. Cell cycle analysis identified a decrease in G0-G1 phase cells and an increase in G2-M phase cells and apoptotic cells, for both EPA and DHA-exposed cells. The d ata show that the presence of n-3 PUFAs in the diet is able to significantl y after the growth rate of the Walker 256 tumour. The involvement of change s in mitochondrial membrane composition and membrane potential have been in dicated for both EPA and DHA, while changes in lipid peroxidation have been identified in the presence of EPA but not of DHA. Copyright (C) 2001 John Wiley & Sons, Ltd.