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Induction of apoptosis in human leukemic cells by the ether lipid 1‐octadecyl‐2‐methyl‐ RAC ‐glycero‐3‐ phosphocholine. A possible basis for its selective action
Author(s) -
Diomede Luisa,
Colotta Francesco,
Piovani Bianca,
Re Fabio,
Modest Edward J.,
Salmona Mario
Publication year - 1993
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910530123
Subject(s) - phosphocholine , cytotoxic t cell , apoptosis , hl60 , programmed cell death , cell culture , chemistry , cytotoxicity , biology , ether , k562 cells , biochemistry , microbiology and biotechnology , phospholipid , in vitro , membrane , genetics , phosphatidylcholine , organic chemistry
Ether‐linked glycerophospholipids (ether lipids, EL) are membrane‐interactive drugs selectively cytotoxic toward neoplastic cells compared with normal cells. No conclusive explanation has yet been provided for this selectivity. We now present data indicating that the drug 1‐octadecyl‐2‐methyl‐ rac ‐glycero‐3‐phosphocholine (ET‐18‐OMe) induces apoptosis, or programmed cell death, in human leukemic cells. Apoptotic death is induced selectively by ET‐18‐OMe in HL60 cells, which are sensitive to the drug's cytotoxic action, but not in the resistant K562 cell line. Enrichment of HL60 cells with cholesterol (HWO‐CHOL cells) significantly protects the cells from the cytotoxic effect and from the induction of apoptosis by ET‐18‐OMe; the percentage of fragmented DNA is only 17% for HL60‐CHOL, compared with 50% in native HL60 cells after exposure to 20 μ ET‐18‐OMe for 24 hr. Our study provides a possible explanation for differences in sensitivity to EL among different cell types and illustrates an indirect interaction of EL with cellular DNA.