Document Detail


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.
MedLine Citation:
PMID:  8416196     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (HL60-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 microns 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.
Authors:
L Diomede; F Colotta; B Piovani; F Re; E J Modest; M Salmona
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  53     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  1993 Jan 
Date Detail:
Created Date:  1993-01-13     Completed Date:  1993-01-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  124-30     Citation Subset:  IM    
Affiliation:
Istituto di Ricerche Farmacologiche Mario Negri, Laboratory for Enzyme Research, Milan, Italy.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cholesterol / analysis
DNA, Neoplasm / analysis,  drug effects
Drug Resistance
Humans
Leukemia, Promyelocytic, Acute / drug therapy*,  pathology
Membrane Lipids / analysis
Phospholipid Ethers / pharmacology*
Phospholipids / analysis
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA41314/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/DNA, Neoplasm; 0/Membrane Lipids; 0/Phospholipid Ethers; 0/Phospholipids; 57-88-5/Cholesterol; 65492-82-2/edelfosine

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