Phospholipid class as a determinant in docosahexaenoic acid's effect on tumor cell viability.
Here we explore how incorporation of the omega-3 fatty acid docosahexaenoic acid (DHA) into murine leukemia cells (T27A) may alter membrane structure and function. When cells were cultured in DHA-supplemented medium, DHA incorporated rapidly and preferentially into phosphatidyl-ethanolamine (PE), with lesser and slower incorporation into phosphatidylcholine (PC). DHA at low concentrations preferred PE over neutral lipids, but in DHA excess accumulation in neutral lipids outstripped that of phospholipids. High DHA levels reduced cell growth in the apparent absence of lipid peroxidation. To study the importance of DHA's phospholipid class, cells were fused with lipid vesicles of either 18:0, 22:6 PE or 18:0, 22:6 PC. DHA-containing PC vesicles produced a dose-dependent decrease in cell viability, whereas PE-containing vesicles had little effect although they appeared more fusogenic. These results provoke the interesting speculation that T27A cells can safely accumulate DHA in PE, but are vulnerable if excessive DHA is incorporated into PC.
Zerouga
M
M
Department of Biology, Indiana University, Purdue University at Indianapolis 46202-5132, USA.
Stillwell
W
W
Stone
J
J
Powner
A
A
Jenski
L J
LJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation; D008563:Membrane Lipids / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D008563:Membrane Lipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D004281:Docosahexaenoic Acids