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Neoplastic cell inhibition with new ether lipid analogs

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Lipids

Abstract

Bioactive phospholipid analogs of platelet-activating factor (PAF) represent a new approach to cancer chemotherapy. Various modifications of the basic structure of PAF lead to different ether lipid (EL) analogs. Data from the evaluation of thioalkyl and amidoalkyl glycerophosphocholine and of glycerophosphoinositol EL analogs against different experimental tumors in vitro (HL60 and K562 human leukemia cells, BG1 and BG3 ovarian adenocarcinomas) are presented. Exclusion of trypan blue after short exposure to the drugs determined cytotoxicity, and a soft agarose clonogenic assay measured the ability of the analogs to inhibit tumor cell proliferation. The thioalkyl EL are very active against the cell lines using both end points, and the amidoalkyl EL showed efficacy against the leukemic cell lines, whereas the phosphoinositol EL are active only at high concentrations. Combined use of EL analogs, which are membrane-interactive, with classical DNA-interactive chemotherapeutic drugs revealed that the combinations have additive antiproliferative effects. These results are promising leads in the development of the anticancer potential of ether lipid analogs.

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Author notes

  1. Michael E. Berens

    Present address: Brain Tumor Research Center, University of California at San Francisco, 94143, San Francisco, CA

Authors and Affiliations

  1. Department of Biochemistry, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina

    Alessandro Noseda & Edward J. Modest

  2. Department of Obstetrics and Gynecology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina

    Michael E. Berens

  3. Oncology Research Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina

    Alessandro Noseda, Michael E. Berens & Edward J. Modest

  4. Department of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina

    Claude Piantadosi

Authors
  1. Alessandro Noseda
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  2. Michael E. Berens
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  3. Claude Piantadosi
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  4. Edward J. Modest
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Cite this article

Noseda, A., Berens, M.E., Piantadosi, C. et al. Neoplastic cell inhibition with new ether lipid analogs. Lipids 22, 878–883 (1987). https://doi.org/10.1007/BF02535548

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  • DOI: https://doi.org/10.1007/BF02535548

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