Neoplastic cell inhibition with new ether lipid analogs.
Bioactive phospholipid analogs of platelet-activating factor (PAF) represent a new approach to cancer chemotherapy. Various modifications of the basic structure of PAF lead to different ether lipid (EL) analogs. Data from the evaluation of thioalkyl and amidoalkyl glycerophosphocholine and of glycerophosphoinositol EL analogs against different experimental tumors in vitro (HL60 and K562 human leukemia cells, BG1 and BG3 ovarian adenocarcinomas) are presented. Exclusion of trypan blue after short exposure to the drugs determined cytotoxicity, and a soft agarose clonogenic assay measured the ability of the analogs to inhibit tumor cell proliferation. The thioalkyl EL are very active against the cell lines using both end points, and the amidoalkyl EL showed efficacy against the leukemic cell lines, whereas the phosphoinositol EL are active only at high concentrations. Combined use of EL analogs, which are membrane-interactive, with classical DNA-interactive chemotherapeutic drugs revealed that the combinations have additive antiproliferative effects. These results are promising leads in the development of the anticancer potential of ether lipid analogs.
Noseda
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Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.
Berens
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ME
Piantadosi
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C
Modest
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EJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002460:Cell Line; D003603:Cytotoxins / Q000494:pharmacology; D005995:Glyceryl Ethers / Q000494:pharmacology*; D006801:Humans; D010742:Phospholipid Ethers / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D003603:Cytotoxins; D005995:Glyceryl Ethers; D010742:Phospholipid Ethers