Synthetic phosphoethanolamine has in vitro and in vivo anti-leukemia effects

Abstract

Background: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.Methods: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.Results: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.Conclusion: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.

Potential antitumor activity of novel DODAC/PHO-S liposomes

“…A 1 M stock solution of PHO-S was prepared in water and stored at room temperature for in vitro assays. [4][5][6][7][8] DODAC was obtained from DODAB (Sigma-Aldrich Co., St Louis, MO, USA) by ion exchange. Primarily, DODAC powder was weighed and suspended in 10 mL of water in order to obtain final concentrations of 0.3, 0.6, 1.0, 1.3, 1.6, and 2.0 mM.…”

“…[4][5][6][7][8] Hepa1c1c7 was added in this study with the aim of assessing the potential anticancer capability of DODAC/PHO-S liposomes and PHO-S in hepatocarcinoma cells that enables easy reproducibility for in vivo studies. Ethical approval for the use of human cells was not sought.…”

“…In vitro antiangiogenic activity assays showed that PHO-S inhibits endothelial cell proliferation, migration, and tube formation. 6,7 These changes, associated with apoptotic effect, reflected an increased expression of active forms of caspase 3. 8 However, the molecular mechanism responsible for the antitumor properties of PHO-S is still under investigation.…”

“…[4][5][6][7] The antineoplastic phospholipids are a new class of antitumor agents, which can cause collateral effects, such as gastrointestinal toxicity, hemolysis, and liver and renal dysfunction. These effects are attributed to agents such as edelfosine, ilmofosine, and miltefosine.…”

A "miracle" cancer drug in the era of social media: A survey of Brazilian oncologists' opinions and experience with phosphoethanolamine

“…A chemistry professor and his team in one of the campuses of the University of São Paulo have studied the drug in its synthetic version. Potential antineoplastic effects have been demonstrated in a few preclinical studies using cell lines [2][3][4][5] and mice models; 6,7 nonetheless, no appropriate safety studies have been carried out in humans. That has not kept the research team from manufacturing the substance in one of the chemistry laboratories at the university and distributing it to an increasing number of patients over the years.…”