The induction of apoptosis is a common feature of the cytotoxic action of ether-linked glycerophospholipids in human leukemic cells.
The ability of 2 recent ether-lipid derivatives, aza-phospholipids BN52205 and BN52211, to induce apoptosis in different leukemia cell lines was investigated using I-octadecyl-2-methyl-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 microM of drug. The 2 aza-derivatives were 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-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.
Diomede
L
L
Istituto di Ricerche Farmacologiche Mario Negri, Laboratory for Enzyme Research, Milan, Italy.
Piovani
B
B
Re
F
F
Principe
P
P
Colotta
F
F
Modest
E J
EJ
Salmona
M
M
D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D003603:Cytotoxins; D004249:DNA Damage; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000188:drug therapy*; D008246:Lysophospholipids / Q000633:toxicity*; D010712:Phosphatidic Acids / Q000737:chemistry / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D003603:Cytotoxins; D008246:Lysophospholipids; D010712:Phosphatidic Acids; C072522:BN 52205; C072525:BN 52211