Docosahexaenoic acid in phosphatidylcholine mediates cytotoxicity more effectively than other omega-3 and omega-6 fatty acids

We reported previously that docosahexaenoic acid (22:6)-containing phosphat idylcholine (PC), but not oleic acid-containing PC nor 22:6-containing phos phatidylethanolamine, is toxic to tumor cells in vitro. To test whether oth er polyunsaturated fatty acids share 22:6's cytotoxic activity, we treated cultured T27A murine leukemia cells with PC liposomes composed of stearic a cid in the sn-1 position and alpha-linolenic acid (alpha-18:3), arachidonic acid (20:4), or eicosapentaenoic acid (20:5) in the sn-2 position. PC cont aining 22:6 in both positions was also tested. Following treatment, the cel ls were monitored for fatty acid composition, liposome uptake and viability . Here we demonstrate that cytotoxicity is unique to 22:6-containing PCs an d is not shared by PCs with other polyunsaturated omega-3 and omega-6 fatty acids. Because PCs with fatty acids other than 22:6 were taken up by cells but did not kill the cells, we propose that 22:6-containing PCs incorporat ed into cellular membranes produce unique changes in the membrane structure incompatible with cell survival. PC liposomes containing 22:6 are potentia l drug delivery vehicles that may, by virtue of their cytotoxicity, serve c oncomitantly as adjunct cancer therapy. (C) 1998 Elsevier Science Ireland L td. All rights reserved.