INHIBITION OF CELL DIVISION BUT NOT NUCLEAR DIVISION BY 1- O -OCTADECYL-2- O -METHYL- Sn -GLYCERO-3-PHOSPHOCHOLINE

• Published in: Cell biology international 1999-12, Vol.23 (12), p.817-828
• Main Authors: Pushkareva, Marina Y, Janoff, Andrew S, Mayhew, Eric
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; cell cycle; Cell Cycle - drug effects; Cell Division - drug effects; Cell Nucleus - pathology; Cell Nucleus - physiology; Cyclin B - drug effects; Cyclin B - metabolism; Cyclin B1; cytokinesis; DNA Fragmentation - drug effects; Dose-Response Relationship, Drug; ET-18-OCH3; Humans; inhibition; Liposomes - pharmacology; Lysophosphatidylcholines - pharmacology; Mice; Mitosis; Phospholipid Ethers - pharmacology; Tumor Cells, Cultured
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1006/cbir.1999.0478

1- O -Octadecyl-2- O -methyl-glycero-3-phosphocholine (ET-18-OCH3) selectively inhibits the growth of cancer cells. Here we show that in some cell types ET-18-OCH3and liposome-associated ET-18-OCH3inhibit 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-OCH3-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)-α (Pushkareva et al., 2000). Furthermore, treatment of cells with ET-18-OCH3results 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.