Differential roles of internal and terminal double bonds in docosahexaenoic acid: Comparative study of cytotoxicity of polyunsaturated fatty acids to HT-29 human colorectal tumor cell line

The role of the double bonds in docosahexaenoic acid (22:6Δ4,7,10,13,16,19; DHA) in cytotoxic lipid peroxidation was studied in a superoxide dismutase-defective human colorectal tumor cell line, HT-29. In a conventional culture, DHA and other polyunsaturated fatty acids (PUFAs) were found to induce acute lipid peroxidation and subsequent cell death. PUFAs that lack one or both the terminal double bonds (Δ19 and Δ4) but share Δ7,10,13,16 such as 22:5Δ7,10,13,16,19, 22:5Δ4,7,10,13,16, and 22:4Δ7,10,13,16 were more effective than DHA. Lipid peroxidation and cell death were completely inhibited, except by 22:4Δ7,10,13,16 when radical-mediated reactions were suppressed by culturing cells in 2% O2 in the presence of vitamin E. DHA and C22:5 PUFAs but not 22:4Δ7,10,13,16 were efficiently incorporated in phosphatidylinositol, regardless of the culturing conditions. These and other results suggested that the internal unsaturations Δ7,10,13,16 were sensitive to lipid peroxidation, whereas the terminal ones Δ19 and Δ4 appeared to be involved in assimilation into phospholipids.