INHIBITORY EFFECTS OF N-3 POLYUNSATURATED FATTY-ACIDS ON SIGMOID COLON-CANCER TRANSFORMANTS

Various types of polyunsaturated fatty acids (PUFAs) have been suggest ed to exert different effects on the colon in terms of promotion or in hibition of tumor development, Results of in vitro and in vivo studies are, however, inconsistent and it remains unclear whether or not the cellular effects of PUFAs change along with the malignant transformati on of colonic cells. In this study, we used the NIH3T3 cell line and i ts SIC (sigmoid colon cancer) oncogene transformants to compare the ef fects of PUFAs on the proliferation of non-malignant and malignant cel ls. We also determined the cellular-utilization of fatty acids in medi a by a high-performance liquid chromatography method. The addition of exogenous arachidonic acid (ARA: an n-6 fatty acid), eicosapentaenoic acid (EPA, n-3), and docosahexaenoic acid (DHA, n-3) exerted different effects on NIH3T3 cells, and on SIC transformants, in which selective inhibitory effects were observed al media concentrations ranging from 10 to 20 mu g/ml. In cells cultured in media supplemented with EPA or DHA at a concentration of 2 mu g/ml, which had no effect an cell prol iferation, the cellular utilization of linoleic acid (n-6), a precurso r of n-3 fatty acids, was inhibited, This inhibition was stronger in S IC transformants than in NIH3T3 cells (P < 0.05). There was no differe nce in the utilization of fatty acids between the two cell lines cultu red in media supplemented with ARA, We conclude that the cellular resp onse to exogenous long-chain PUFAs is modified during the course of ma lignant transformation, and that EPA and DHA (n-3 PUFAs) appear to hav e specific inhibitory effects on cancer cells and may thus enhance the host defense against colon cancer.