Early and selective induction of apoptosis in human leukemic cells by the alkyl-lysophospholipid ET-18-OCH3.
We have found that the alkyl-lysophospholipid 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) was able to induce apoptosis in human promyelocytic HL-60 leukemic cells, as evidenced by the internucleosomal degradation of the cellular DNA into the characteristic 180-200 bp DNA fragments. This effect was observed after short periods of cell incubation (6 h) with low doses of ET-18-OCH3 (3 micrograms/ml). Furthermore, we found that ET-18-OCH3 also induced rapidly apoptosis in human promonocytic U937 leukemic cells. In contrast, 3T3 fibroblasts were resistant to the alkyl-lysophospholipid. ET-18-OCH3 induced apoptotic cell death of tumor epithelial-like HELA cells, but this process required prolonged times of incubation. These data demonstrate that ET-18-OCH3 promotes a rapid and selective programmed cell death in human leukemic cells, providing an explanation to the previously described cytotoxic effects of this compound on leukemic cells.
Mollinedo
F
F
Centro de Investigaciones Biológicas, C.S.I.C., Madrid, Spain.
Martínez-Dalmau
R
R
Modolell
M
M
D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010742:Phospholipid Ethers / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
C076164:3-octadecyl-2-methylglycero-1-phosphocholine; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D010742:Phospholipid Ethers; D013936:Thymidine