Role of cell cholesterol in modulating antineoplastic ether lipid uptake, membrane effects and cytotoxicity

L. Diomede, A. Bizzi, A. Magistrelli, E. J. Modest, M. Salmona, A. Noseda

Research output: Contribution to journalArticlepeer-review

Abstract

Membrane-interactive ether lipids (EL) exert toxic and antiproliferative effects on cancer cells in vitro. They appear to be selectively more toxic to cancer cells than to normal cells and thus they are ideal candidates for bone-marrow purging procedures. However, no conclusive explanation has yet been provided for this property. We now present some data indicating that the cholesterol concentration in the incubation medium modulates EL toxicity against the HL60 leukemic cell line in vitro. Furthermore, model membranes richer in cholesterol take up EL more slowly, and cell cholesterol enrichment of HL60 cells counteracts EL biophysical membrane interaction, but not toxicity, in our experimental model. However, the K562 cell line, a leukemia line less sensitive to EL toxic action, has higher levels of cell cholesterol. Our data provide evidence to explain differences in sensitivity to EL among different cell types and contribute to the understanding of the mechanism of action of EL.

Original languageEnglish
Pages (from-to)341-346
Number of pages6
JournalInternational Journal of Cancer
Volume46
Issue number2
DOIs
Publication statusPublished - 1990

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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