Alkylphosphocholines: Effects on human leukemic cell lines and normal bone marrow cells.

Abstract

The anti-leukemic activity of a series of alkylphosphocholines (APCs) was studied against a panel of human leukemic cell lines (HL-60, K-562, Reh, MOLT-4, Jurkat, Ramos and Raji). Cytotoxic efficacy was measured by the MTT cell survival assay. All cell lines were found to be sensitive, except the multipotential CML-derived K-562 cell line. Flow cytometry of HL-60 cells showed a significant decrease of cells in S phase and the formation of a sub-G fraction. DNA fragmentation typical for programmed cell death was detected by DNA gel electrophoresis in these cells but not in any of the other leukemic lines. At concentrations below the cytotoxic range, mitogenic effects were seen in HL-60 cells after 14-hr exposure. Colony formation by K-562 cells revealed an augmented clonogenicity after exposure to APC with a short alkyl chain. In contrast, cells of lymphoid origin did not undergo DNA fragmentation or show mitogenic stimulation after exposure to APC. Normal bone marrow cells were also investigated for mitogenic and genotoxic effects. No decrease was found in the number of hematopoietic progenitors in long-term bone marrow cell cultures after exposure to APC. On the contrary, a significant increase was found after short exposure. Dodecylphosphocholine, hexadecylphosphocholine (HPC) and (octadecyl-[2-(N-methylpiperidino)-ethyl]phosphate exhibited a mild clastogenicity at equimolar high doses on murine bone marrow cells in vivo, which is unusual for the majority of classical DNA-interacting anti-cancer drugs. In conclusion, APCs are agents with a broad spectrum of in vitro anti-leukemic effects, which lack hematological toxicity.

• Authors: S M Konstantinov, M Topashka-Ancheva, A Benner, M R Berger
• Journal: International journal of cancer (Int J Cancer) Vol. 77 Issue 5 Pg. 778-86 (Aug 31 1998) ISSN: 0020-7136 [Print] United States
• PMID: 9688313 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Mutagens
• Phosphorylcholine
• Mitomycin

Topics

• Alkylation
• Animals
• Antineoplastic Agents (toxicity)
• Apoptosis (drug effects)
• Bone Marrow Cells (cytology, drug effects)
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Cells, Cultured
• DNA Fragmentation
• Female
• Flow Cytometry
• HL-60 Cells (drug effects)
• Humans
• Jurkat Cells (drug effects)
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Mice
• Mice, Inbred Strains
• Mitomycin (toxicity)
• Mutagens (toxicity)
• Phosphorylcholine (analogs & derivatives, toxicity)
• Structure-Activity Relationship
• Tumor Cells, Cultured