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Ether lipid derivatives: Antineoplastic activity in vitro and the structure-activity relationship

  • Papers from the Brian L. Walker Memorial Symposium on Lipids and Cancer Presented at the 76th AOCS Annual Meeting in Philadelphia, Pennsylvania, May 1985
  • Published:
Lipids

An Erratum to this article was published on 01 May 1986

Abstract

The antineoplastic activity of two ether lipid derivatives, the alkyl-lysophospholipid derivative (ALP) ET-18-OCH3 and the ether-linked lipoidal amine CP-46,665 was tested in a human tumor clonogenic assay (HTCA) in vitro. CP-46,665 suppresed the colony formation of various human tumors with a slight dose response relation after 1 hr incubation and with a clear optimum (85% response rate) after continuous exposure in the higher dose range tested (10 μg/ml). ET-18-0CH3 did not have substantial activity after 1 hr of incubation. However, when continuous exposure to the compound was used, ET-18-OCH3 seemed to have a modest dose response effect and yielded a response in about 60% of the tumor cell samples tested in the higher dose range (10 μg/ml). Thus, both compounds have in vitro antitumor activity in the HTCA within a dose range of 1–10 μg/ml, especially during continuous exposure. The tumor specific type activity was found in breast cancer, ovarian cancer, lung cancer and mesothelioma. Both compounds caused decreases in colony formation down to the 0%, 2% and 4% levels. In a comparison of specimens in which both compounds were used, only one of five times showed a discordance in sensitivity or resistance; therefore the compounds appear similar in their in vitro activity.

In a second set of experiments we tested the structure-activity relationship among a variety of ALP in the [3H]thymidine incorporation assay after incubation with HL-60 leukemic blasts and other neoplastic cells from human origin. From these studies it can be concluded that in the ALP the alkyl linkage in the sn-1 position is a necessary prerequisite for cytotoxicity; furthermore, in the majority of tumors tested the substitution of the sn-2 position to prevent reacylation of the molecule is necessary for cytotoxicity.

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Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine I, Technical University, Ismaninger Str. 22, Munich, Federal Republic of Germany

    Wolfgang E. Berdel, Hans D. Schick, Ulrich Fink, Anneliese Reichert & Johann Rastetter

  2. Department of Medicine, Division of Oncology, University of Texas, Health Science Centre at San Antonio, San Antonio, Texas

    Daniel D. Von Hoff

  3. Cancer Therapy and Research Center of South Texas, San Antonio, Texas

    Daniel D. Von Hoff

  4. Division of Hematology and Oncology, Department of Medicine, University, Gottingen, Federal Republic of Germany

    Clemens Unger

  5. Max Planck Institute for Biophysical Chemistry, Gottingen, Federal Republic of Germany

    Hansjorg Eibl

Authors
  1. Wolfgang E. Berdel
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  2. Daniel D. Von Hoff
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  4. Hans D. Schick
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  5. Ulrich Fink
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  6. Anneliese Reichert
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  7. Hansjorg Eibl
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  8. Johann Rastetter
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Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/BF02535704.

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Berdel, W.E., Von Hoff, D.D., Unger, C. et al. Ether lipid derivatives: Antineoplastic activity in vitro and the structure-activity relationship. Lipids 21, 301–304 (1986). https://doi.org/10.1007/BF02536417

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  • DOI: https://doi.org/10.1007/BF02536417

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