Comparison of selective cytotoxicity of alkyl lysophospholipids

W. R. Vogler, A. C. Olson, S. Okamoto, M. Shoji, R. L. Raynor, J. F. Kuo, W. E. Berdel, H. Eibl, J. Hajdu, H. Nomura

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Abstract

Alkyl lysophospholipids have been shown to be cytooxic to a number of neoplastic tissues. One, ET-18-OCH3, has been used to selectively purge leukemic cells from mixtures with normal marrow progenitor cells, in vitro and in vivo. We have measured the 50% inhibitory (IC50) effect of a series of ether, lipids (EL) on leukemic cells (HL60, K562, Daudi, KG-1, KG-1a) and normal marrow progenitor cells. Cells were incubated with varying concentrations of EL for 4 hr and assayed for viability, [3H]thymidine incorporation and clonogenicity in semi-solid media. The effect on protein kinase C (PKC) activity was assayed for each compound. Compounds tested included three glycerophosphocholine analogs-ET-18-OCH3, ET-16-NHCOCH3, and BM 41.440. In addition, a lipoidal amine, CP 46665, an ethyleneglycolphospholipid, AEPL, and four single chain alkylphosphocholine analogs, HePC2, HePC3, HePC4 and HePC6 were also tested. During the period of incubation, the cells remained viable (>70%) as judged by trypan blue dye exclusion. The glycerophosphocholines were the most active and showed the highest therapeutic index. The lipoidal amine was active, but toxic to normal marrow progenitor cells. The ethyleneglycolphospholipid was active against HL60, but not against the other cell lines. The single chain alkylphosphocholine analogs were less active. All of the compounds inhibited PKC activity; however, the glycerophosphocholines were the most inhibitory.

Original languageEnglish
Pages (from-to)1418-1423
Number of pages6
JournalLipids
Volume26
Issue number12
DOIs
Publication statusPublished - 1991 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Cell Biology

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    Vogler, W. R., Olson, A. C., Okamoto, S., Shoji, M., Raynor, R. L., Kuo, J. F., Berdel, W. E., Eibl, H., Hajdu, J., & Nomura, H. (1991). Comparison of selective cytotoxicity of alkyl lysophospholipids. Lipids, 26(12), 1418-1423. https://doi.org/10.1007/BF02536579