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 phosphatidylcholine (PC), but not oleic acid-containing PC nor 22:6-containing phosphatidylethanolamine, is toxic to tumor cells in vitro. To test whether other polyunsaturated fatty acids share 22:6's cytotoxic activity, we treated cultured T27A murine leukemia cells with PC liposomes composed of stearic acid 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 containing 22:6 in both positions was also tested. Following treatment, the cells were monitored for fatty acid composition, liposome uptake and viability. Here we demonstrate that cytotoxicity is unique to 22:6-containing PCs and 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 incorporated into cellular membranes produce unique changes in the membrane structure incompatible with cell survival. PC liposomes containing 22:6 are potential drug delivery vehicles that may, by virtue of their cytotoxicity, serve concomitantly as adjunct cancer therapy.
Department of Biology, Indiana University-Purdue University at Indianapolis, 46202-5132, USA.
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O
Kafrawy
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Zerouga
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Stillwell
L J
LJ
Jenski
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000633:toxicity; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000633:toxicity*; D008081:Liposomes; D010713:Phosphatidylcholines / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D008081:Liposomes; D010713:Phosphatidylcholines; D004281:Docosahexaenoic Acids