Alkylphosphocholines induce apoptosis in HL-60 and U-937 leukemic cells.
Alkylphosphocholines (APC) represent a new group of ether-lipid-related compounds with remarkable activity against transformed cells in vitro and good tolerability in vivo. Their mechanism of action remains unknown. The aim of the present study was to investigate the effects of a series of APC on three human leukemic cell lines: K-562, HL-60, and U-937. The tetrazolium dye-reduction (MTT) assay and cell counting were used to determine the cytotoxicity of the APC used. DNA gel electrophoresis and enzyme-linked immunosorbent assay (ELISA) detection of oligonucleosomes were performed to identify and quantify DNA fragmentation. Electron and phase-contrast microscopy were used to detect morphologic changes specific for programmed cell death. HL-60 and U-937 cells were found to be sensitive, but K-562 cells were relatively resistant to APC exposure. APC with long alkyl chains exerted stronger cytotoxicity than did those with short alkyl chains. DNA fragmentation was found after treatment with APC in HL-60 and U-937 cells but not in K-562 cells. In HL-60 cells the increase in mono- and oligonucleosome formation as measured by ELISA was correlated with the length of the alkyl chains at 14 h of exposure to APC but plateaued at 20 h. The morphologic alterations in HL-60 and U-937 cell lines, such as cell shrinkage, chromatin condensation, and formation of apoptotic bodies, confirmed the induction of apoptosis after APC exposure. It is concluded that programmed cell death plays an important role in the cytotoxicity of APC against certain human leukemic cell lines. The antineoplastic profiles of APC with long alkyl chains render them attractive for further therapeutic application.
Konstantinov
S M
SM
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Bulgaria.
Eibl
H
H
Berger
M R
MR
D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation; D004797:Enzyme-Linked Immunosorbent Assay; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D008854:Microscopy, Electron; D010767:Phosphorylcholine / Q000031:analogs & derivatives*; D013329:Structure-Activity Relationship
D010767:Phosphorylcholine