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 phospholipid activities, such as lipid composition and transportation, contribute to cellular homeostasis in the lifespan of cells. Alterations in phospholipids result in the movement of bilayer lipids and the initiation of coagulation, recognition and internalization. Hexadecylphosphocholine (HePC) exerts antitumor potencies and represents a new class of antitumor agents targeted to the cellular membrane. Human myeloid leukemia cell lines HL-60 and 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 myeloid leukemia HL-60 and K562 cell lines. The contents of membrane phospholipids, including phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylethanolamine (PE), were determined quantitatively with high performance liquid chromatography. The sensitivity of myeloid leukemia HL-60 and K562 cell lines to HePC probably depends on the different distribution of these four phospholipids in the cellular membrane, or on the response of these phospholipids to HePC. The cytosolic free calcium ([Ca++]i) concentration increased by HePC confirmed that [Ca++]i was released from the intracellular calcium pool and is associated with cell differentiation and apoptosis. We investigated the hypothesis that the antiproliferative effect of HePC was mediated through the interference with cellular membrane phospholipids, including choline-containing phospholipids (PC), aminophospholipids (PE and PS) and PI, in eukaryotic cells.
Wang
Y Z
YZ
Institute of Radiation Medicine of AMMS, Beijing, China. wangyz@nic.bmi.ac.cn
Chang
Y B
YB
Xing
C
C
Fu
D
D
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003600:Cytosol; D018922:HL-60 Cells; D006801:Humans; D010743:Phospholipids / Q000378:metabolism*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010743:Phospholipids; D010767:Phosphorylcholine; C039128:miltefosine; D002118:Calcium