Jackson J K, Burt H M, Oktaba A M, Hunter W, Scheid M P, Mouhajir F, Lauener R W, Shen Y, Salari H, Duronio V
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Cancer Chemother Pharmacol. 1998;41(4):326-32. doi: 10.1007/s002800050746.
We investigated the cytotoxic and antiangiogenic activity of the ether lipid, 2'-(trimethylammonio)ethyl 4-(hexadecyloxy)-3(S)-methoxybutane-phosphonate (termed s-phosphonate).
Cytotoxicity was determined using an XTT bioassay. Apoptosis was measured by either DNA fragmentation or immunolabelling techniques. Angiogenesis was measured using the in vivo chorioallantoic membrane (CAM) of the chick embryo.
S-phosphonate was selectively cytotoxic towards the 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 agent at concentrations as high as 50 microM. This selectivity resulted from the induction of apoptosis (or programmed cell death) by s-phosphonate in HL-60 and AML-14 cells but not in 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 s-phosphonate were also the only areas of the membrane in which apoptosis occurred.
We conclude that s-phosphonate selectively induces apoptosis in human leukemic cells and exhibits antiangiogenic and apoptotic activity on the CAM.
我们研究了醚脂2'-(三甲基铵基)乙基4-(十六烷氧基)-3(S)-甲氧基丁烷膦酸酯（称为s-膦酸酯）的细胞毒性和抗血管生成活性。
使用XTT生物测定法测定细胞毒性。通过DNA片段化或免疫标记技术测量细胞凋亡。使用鸡胚的体内绒毛尿囊膜（CAM）测量血管生成。
s-膦酸酯对人白血病细胞系HL-60和AML-14具有选择性细胞毒性，而白血病K-562细胞和小鼠肥大细胞系MC-9在高达50 microM的浓度下对该药物具有抗性。这种选择性是由于s-膦酸酯在HL-60和AML-14细胞中诱导凋亡（或程序性细胞死亡），而在抗性K-562或MC-9细胞中则不然。s-膦酸酯在CAM中诱导局部抗血管生成作用和膜变薄。这种浓度依赖性抗血管生成作用与通过提取的CAM组织中的DNA片段化测量的CAM中的凋亡相关。s-膦酸酯引起的CAM上膜变薄和抗血管生成的局部区域也是膜中发生凋亡的唯一区域。
我们得出结论，s-膦酸酯在人白血病细胞中选择性诱导凋亡，并在CAM上表现出抗血管生成和凋亡活性。
