The induction of apoptosis is a common feature of the cytotoxic action of ether-linked glycerophospholipids in human leukemic cells

Authors

  • Luisa Diombde,

    Corresponding author
    1. Istituto di Ricerche Farmacologiche “Mario Negri”. Laboratory for Enzyme Research and Centro Davide e Catullo Borgomainerio, Milan, Italy
    • Laboratory for Enzyme Research, Instiuto di Ricerche Farmacologiche “Mario Negri,” Via Eritea 62, 20157 Milan, Italy
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  • Bianca Piovani,

    1. Istituto di Ricerche Farmacologiche “Mario Negri”. Laboratory for Enzyme Research and Centro Davide e Catullo Borgomainerio, Milan, Italy
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  • Fabio Re,

    1. Istituto di Ricerche Farmacologiche “Mario Negri”. Laboratory for Enzyme Research and Centro Davide e Catullo Borgomainerio, Milan, Italy
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  • Paola Principe,

    1. Instiut Henri Beaufour, I, avenue des Tropiques, 91952 Les Ulis Cédex, France
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  • Francesco Colotta,

    1. Istituto di Ricerche Farmacologiche “Mario Negri”. Laboratory for Enzyme Research and Centro Davide e Catullo Borgomainerio, Milan, Italy
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  • Edward J. Modest,

    1. Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
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  • Mario Salmona

    1. Istituto di Ricerche Farmacologiche “Mario Negri”. Laboratory for Enzyme Research and Centro Davide e Catullo Borgomainerio, Milan, Italy
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Abstract

The ability of 2 recent ether-lipid derivatives, aza-phospholipids BN52205 and BN522II, to induce apoptosis in different leukemia cell lines was investigated using I-octadecyl-2-methly-rac-glycero-3-phosphocholine (ET-18-OCH3) as a positive control. HL60, K562, Molt-4 and U937 cells were exposed for 24 hr to 20 μM of drug. The 2 aza-derivatives were as cytotoxic as ET-18-OCH3: BN52205 and BN522II selectively induced apoptotic death in HL60, Molt-4 and U937 cells, but not in the KS62-resistant cell line. Around 50% of DNA was fragmented in HL60 cells after exposure to the aza-derivatives, and 34% and 20% of DNA was fragmented in Molt-4 and U937 cells respectively. Similar results were obtained when cells were exposed to ET-18-OCH3. Our data confirm that ether lipids induce apoptosis in a variety of human leukemic cells, providing a possible explanation for their selectivity and mechanism of action.

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