The antineoplastic ether lipid, s-phosphonate, selectively induces apoptosis in human leukemic cells and exhibits antiangiogenic and apoptotic activity on the chorioallantoic membrane of the chick embryo

Introduction: We investigated the cytotoxic and antiangiogenic activity of the ether lipid. 2'-(trimethylammonio)ethyl 4-(hexadecyloxy)-3(S)-methoxy-butane-phosphonate (termed s-phosphonate). Method: Cytotoxicity was determined using an XTT bioassay. Apoptosis was measured bq tither DNA fragmentation or immunolabelling techniques. Angiogenesis was measured using the in vivo chorioallantoic membrane (CAM) of the chick embryo. Results: s-phosphonate was selectively cytotoxic towards human leukemic cell lines, HL-60 and AML-14, whereas leukemic k-562 cells and the murine mast cell line, MC-9, were resistant to this gent at concentrations as high as 50 mu M. This selectivity resulted from the induction of apoptosis (or programmed cell death) bq s-phosphonate in HL-60 and AML-14 cells but not ill resistant K-562 or MC-9 cells, S-phosphonate induced localized antiangiogenic effects and membrane thinning in the CAM. This concentration-dependent antiangiogenic effect was associated with apoptosis in the CAM as measured by DNA fragmentation in extracted CAM tissue. The localized areas of membrane thinning and antiangiogenesis on the CAM caused by 5-phosphonate were also the only al-eas of the membrane in which apoptosis occurred. Conclusion: We conclude that s-phosphonate selectively induces apoptosis in human leukemic cells and exhibits antiangiogenic and apoptotic activity on the CAM.