1] Biochemistry and Biophysical Laboratory, Institute Butantan, São Paulo, Brazil [2] Experimental Physiopathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Br J Cancer. 2013 Nov 26;109(11):2819-28. doi: 10.1038/bjc.2013.510. Epub 2013 Nov 7.
We recently showed that synthetic phosphoethanolamine reduces tumour growth and inhibits lung metastasis in vivo. Here, we investigated its anti-leukaemia effects using acute promyelocytic leukaemia (APL) as a model.
Cytotoxic effects of Pho-s on leukaemia cells were evaluated by MTT assay. Leukaemic cells obtained from hCG-PML-RARa transgenic mice were transplanted to NOD/SCID mice. After the animals were diagnosed as leukaemic, treatment started with Pho-s using all-trans retinoid acid or daunorubicin as positive control or and saline control. Cell morphology and immunophenotyping were used to detect the undifferentiated blast cells in the spleen, liver and bone marrow. The induction of apoptosis in vitro and in malignant leukaemic clones was evaluated.
Synthetic phosphoethanolamine is cytotoxic and induces apoptosis through the mitochondrial pathway in vitro to leukaemia cell lines. In vivo Pho-s exhibits anti-proliferative effects in APL model reducing the number of CD117(+) and Gr-1(+) immature myeloid cells in the BM, spleen and liver. Synthetic phosphoethanolamine impairs the expansion of malignant clones CD34(+)/CD117(+), CD34(+) and Gr-1(+) in the BM. In addition, Pho-s induces apoptosis of immature cells in the spleen and liver, a notable effect.
Synthetic phosphoethanolamine has anti-leukaemic effects in an APL model by inhibiting malignant clone expansion, suggesting that it is an interesting compound for leukaemia treatment.
我们最近发现合成的磷酸乙醇胺能够在体内减少肿瘤生长并抑制肺转移。在这里，我们以急性早幼粒细胞白血病（APL）为模型研究了其抗白血病作用。
用 MTT 法评估 Pho-s 对白血病细胞的细胞毒性作用。从 hCG-PML-RARa 转基因小鼠中获得白血病细胞，然后将其移植到 NOD/SCID 小鼠中。在动物被诊断为白血病后，开始用 Pho-s 治疗，并用全反式维甲酸或柔红霉素作为阳性对照或生理盐水对照。使用细胞形态学和免疫表型检测脾、肝和骨髓中未分化的原始细胞。评估体外和恶性白血病克隆中的细胞凋亡诱导作用。
合成的磷酸乙醇胺在体外对白血病细胞系具有细胞毒性，并通过线粒体途径诱导细胞凋亡。在体内，Pho-s 在 APL 模型中表现出抗增殖作用，减少 BM、脾和肝中 CD117(+)和 Gr-1(+)幼稚髓样细胞的数量。合成的磷酸乙醇胺损害 BM 中恶性克隆 CD34(+)/CD117(+)、CD34(+)和 Gr-1(+)的扩增。此外，Pho-s 还诱导脾和肝中幼稚细胞的凋亡，这是一个显著的作用。
合成的磷酸乙醇胺通过抑制恶性克隆扩增在 APL 模型中具有抗白血病作用，表明它是一种有前途的白血病治疗化合物。
