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 activit y of the ether lipid. 2'-(trimethylammonio)ethyl 4-(hexadecyloxy)-3(S) -methoxy-butane-phosphonate (termed s-phosphonate). Method: Cytotoxici ty was determined using an XTT bioassay. Apoptosis was measured bq tit her 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 huma n 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 co ncentrations as high as 50 mu M. This selectivity resulted from tile i nduction of apoptosis (or programmed cell death) bq s-phosphonate in H L-60 and AML-14 cells but not ill resistant K-562 or MC-9 cells, S-pho sphonate induced localized antiangiogenic effects and membrane thinnin g in the CAM. This concentration-dependent antiangiogenic effect was a ssociated with apoptosis in the CAM as measured by DNA fragmentation i n extracted CAM tissue. The localized areas of membrane thinning and a ntiangiogenesis on the CAM caused by 5-phosphonate were also the only al-eas of the membrane in which apoptosis occurred, Conclusion: We con clude that s-phosphonate selectively induces apoptosis in human leukem ic cells and exhibits antiangiogenic and apoptotic activity on the CAM .