The interference effects of hexadecylphosphocholine on proliferation and membrane phospholipid metabolism in human myeloid leukemia cell lines

Membrane phospholipids are important regulators of cellular function. The p hospholipid activities, such as lipid composition and transportation, contr ibute to cellular homeostasis in the lifespan of cells. Alterations in phos pholipids result in the movement of bilayer lipids and the initiation of co agulation, recognition and internalization. Hexadecylphosphocholine (HePC) exerts antitumor potencies and represents a new class of antitumor agents t argeted to the cellular membrane. Human myeloid leukemia cell lines HL-60 a nd K562 employed in this study were inhibited by HePC in vitro. The results indicate that the HL-60 cell line was sensitive, while K562 was resistant to HePC. Synthetic HePC is an alkyllysophospholipid analog which interacted with the cell membrane, thereby altering lipid composition and metabolism of membrane phospholipids and modulating intracellular calcium in human mye loid leukemia HL-60 and K562 cell lines. The contents of membrane phospholi pids, including phosphatidylinositol (PI), phosphatidylcholine (PC), phosph atidylserine (PS) and phosphatidylethanolamine (PE), were determined quanti tatively with high performance liquid chromatography. The sensitivity of my eloid leukemia HL-60 and K562 cell lines to HePC probably depends on the di fferent distribution of these four phospholipids in the cellular membrane, or on the response of these phospholipids to HePC. The cytosolic free calci um ([Ca++]i) concentration increased by HePC confirmed that [Ca++]i was rel eased from the intracellular calcium pool and is associated with cell diffe rentiation and apoptosis. We investigated the hypothesis that the antiproli ferative effect of HePC was mediated through the interference with cellular membrane phospholipids, including choline-containing phospholipids (PC), a minophospholipids (PE and PS) and PI, in eukaryotic cells.