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Alkylphosphocholines: Effects on human leukemic cell lines and normal bone marrow cells
Author(s) -
Konstantinov S. M.,
TopashkaAncheva M.,
Benner A.,
Berger M. R.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980831)77:5<778::aid-ijc18>3.0.co;2-y
Subject(s) - cytotoxic t cell , bone marrow , cell culture , microbiology and biotechnology , jurkat cells , dna fragmentation , haematopoiesis , cell growth , apoptosis , chemistry , raji cell , flow cytometry , cell , biology , in vitro , cancer research , t cell , immunology , programmed cell death , stem cell , biochemistry , immune system , genetics
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 1 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. Int. J. Cancer, 77:778–786, 1998. © 1998 Wiley‐Liss, Inc.