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Cytotoxicity of thioether-lysophospholipids in leukemias and tumors of human origin.

Abstract
Thioether-lysophospholipids inhibited the in vitro incorporation of [3H]thymidine into blasts of 8 leukemias, lymphocytes of 3 chronic lymphocytic leukemias, and cells of 12 different solid tumors of human origin. This effect correlated with trypan blue dye exclusion, which was used to assess cell damage. Scanning electron microscopy revealed severe membrane destruction after incubation with thioether-lysophospholipids. Cytostatic and cytotoxic effects of thioether-lysophospholipids were dependent on dosage and incubation time. Destruction of leukemic blasts was completed with greater than or equal to 5 micrograms/ml after an incubation of greater than or equal to 48 hr, but 10 to 20 micrograms/ml were necessary in solid tumors. Ester-linked 2-lysophosphatidylcholine was ineffective in the same dose range, which points to the requirement of the alkyl moiety in SN1 of the molecule for the antineoplastic properties of lysophospholipid analogues.
AuthorsW E Berdel, M Fromm, U Fink, W Pahlke, U Bicker, A Reichert, J Rastetter
JournalCancer research (Cancer Res) Vol. 43 Issue 11 Pg. 5538-43 (Nov 1983) ISSN: 0008-5472 [Print] United States
PMID6577950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Lysophospholipids
  • Phospholipids
  • Sulfides
Topics
  • Adenocarcinoma (physiopathology)
  • Cell Line
  • Cell Survival (drug effects)
  • DNA Replication (drug effects)
  • Drug Evaluation, Preclinical
  • Humans
  • Kidney Neoplasms (physiopathology)
  • Kinetics
  • Leukemia, Myeloid (physiopathology)
  • Leukemia, Myeloid, Acute (physiopathology)
  • Lymphoma (physiopathology)
  • Lysophospholipids
  • Neoplasms (physiopathology)
  • Phospholipids (toxicity)
  • Structure-Activity Relationship
  • Sulfides

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