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

研究成果: Article

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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.

元の言語English
ページ(範囲)1418-1423
ページ数6
ジャーナルLipids
26
発行部数12
DOI
出版物ステータスPublished - 1991 12 1
外部発表Yes

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