Inhibition of cell division but not nuclear division by 1-O- octadecyl-2-O-methyl-Sn-glycero-3-phosphocholine.
1-O-Octadecyl-2-O-methyl-glycero-3-phosphocholine (ET-18-OCH(3)) selectively inhibits the growth of cancer cells. Here we show that in some cell types ET-18-OCH(3)and liposome-associated ET-18-OCH(3)inhibit cell division without concurrent inhibition of nuclear division, leading to multinucleate cell formation, and cell death through apoptosis. Cell cycle analysis revealed that ET-18-OCH(3)-treated U-937 cells continued to move through the cell cycle, but many cells were not able to divide and instead accumulated as tetraploid cells or octaploid cells in the G0/G1 phase of the cell cycle. Inhibition of cytokinesis has been shown to be paralleled by activation of U-937 cells, including upregulation of some cell-surface markers, acquisition of phagocytic activity, and secretion of tumor necrosis factor (TNF)-alpha (Pushkareva et al., 2000). Furthermore, treatment of cells with ET-18-OCH(3)results in the accumulation of apoptotic cells in time- and dose-dependent manner. It is possible that inhibition of cytokinesis may be related to cytoskeletal effects.
Pushkareva
M Y
MY
The Liposome Company, Princeton, New Jersey 08540, USA. mpushkar@lipo.com
Janoff
A S
AS
Mayhew
E
E
D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002467:Cell Nucleus / Q000473:pathology / Q000502:physiology*; D019926:Cyclin B / Q000187:drug effects / Q000378:metabolism; D056744:Cyclin B1; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008081:Liposomes / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D051379:Mice; D008938:Mitosis; D010742:Phospholipid Ethers / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; D019926:Cyclin B; D056744:Cyclin B1; D008081:Liposomes; D008244:Lysophosphatidylcholines; D010742:Phospholipid Ethers; C026659:edelfosine