THE INDUCTION OF APOPTOSIS IS A COMMON FEATURE OF THE CYTOTOXIC ACTION OF ETHER-LINKED GYLCEROPHOSPHOLIPIDS IN HUMAN LEUKEMIC-CELLS

The ability of 2 recent ether-lipid derivatives, aza-phospholipids BN5 2205 and BN52211, to induce apoptosis in different leukemia cell lines was investigated using 1-octadecyl-2-methyl-rac-glycero-3-phophocholi ne (ET-18-OCH3) as a positive control. HL60, K562, Molt-4 and U937 cel ls were exposed for 24 hr to 20 mu M of drug. The 2 aza-derivatives we re as cytotoxic as ET-18-OCH3:BN52205 and BN52211 selectively induced apoptotic death in HL60, Molt-4 and U937 cells, but not in the K562-re sistant cell line. Around 50% of DNA was fragmented in HL60 cells afte r exposure to the aza-derivatives, and 34% and 20% of DNA was fragment ed in Molt-4 and U937 cells respectively. Similar results were obtaine d when cells were exposed to ET-18-OCH3. Our data confirm that ether l ipids induce apoptosis in a variety of human leukemic cells, providing a possible explanation for their selectivity and mechanism of action. (C) 1994 Wiley-Liss, Inc.