The effect of phosphoethanolamine intake on mortality and macrophage activity in mice with solid ehrlich tumors

Arruda, Maria Sueli Parreira de; Corrêa, Mara Adriana; Venturini, James; Félix, Maira Camila; Rosis, Ana Maria Bormio De; Galhiane, Mário Sérgio; Chierice, Gilberto Orivaldo; Costa, Maria Renata Sales Nogueira

doi:10.1590/s1516-89132011000600016

Cited by 6 publications

(8 citation statements)

References 22 publications

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“…The general information of the selected articles is presented in Tables I and II. Several studies of PHOS-S have been performed. This substance has been linked to anticarcinogenic effects and reportedly alters the cell metabolism of the immune response (Arruda et al, 2011), elicits antitumor effects (Ferreira et al, 2011(Ferreira et al, , 2012a(Ferreira et al, ,b, 2013a, induces apoptosis in cells (Ferreira et al, 2011(Ferreira et al, , 2012a(Ferreira et al, ,b, 2013a, elicits antileukemic effects (Ferreira et al, 2013c), possesses antiangiogenic (Ferreira et al, 2013b) and antimetastatic activity (Ferreira et al, 2011(Ferreira et al, , 2013b, and, conversely, stimulates tumor proliferation (KanoSueoka et al, 1979).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, the histopathology of the excised tumors showed greater cell cohesion of tumor cells retrieved from mice treated with PHOS-S (Arruda et al, 2011).…”

Section: Alterations In the Cells Of The Immune Responsementioning

confidence: 97%

“…These experiments were performed to assess the ability of the compound to inhibit tumor growth by altering the activity of these cells (Arruda et al, 2011).…”

Section: Alterations In the Cells Of The Immune Responsementioning

confidence: 99%

“…The researchers surgically removed the inoculated tumors (after a period of growth) and washed the abdominal cavity to remove peritoneal macrophages. The macrophages were then subjected to the following assays: spreading test and calculation of H 2 O 2 and NO (substances involved in tumor progression and dispersion) (Arruda et al, 2011).…”

Section: Alterations In the Cells Of The Immune Responsementioning

confidence: 99%

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Synthetic phosphoethanolamine: the state of the art of scientific production

Anastácio

Delmaschio

Oliveira

et al. 2018

Braz. J. Pharm. Sci.

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Section: Resultsmentioning

confidence: 99%

“…Moreover, the histopathology of the excised tumors showed greater cell cohesion of tumor cells retrieved from mice treated with PHOS-S (Arruda et al, 2011).…”

Section: Alterations In the Cells Of The Immune Responsementioning

confidence: 97%

“…These experiments were performed to assess the ability of the compound to inhibit tumor growth by altering the activity of these cells (Arruda et al, 2011).…”

Section: Alterations In the Cells Of The Immune Responsementioning

confidence: 99%

Section: Alterations In the Cells Of The Immune Responsementioning

confidence: 99%

See 2 more Smart Citations

Synthetic phosphoethanolamine: the state of the art of scientific production

Anastácio

Delmaschio

Oliveira

et al. 2018

Braz. J. Pharm. Sci.

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“…In six articles, Chierice and coworkers reported the effects of syn-phospho on cytotoxicity and xenograft tumor rodent assays. [5][6][7][8][9][10] It is of note that in five of these six studies the authors did not declare the purity of the test compound, [5][6][7]9,10 and in one study they informed that syn--phospho (analyzed by high-performance liquid chromatography) was 99% pure. 8 A Nuclear Magnetic Resonance (NMR) analysis conducted by an independent laboratory (University of Campinas -Unicamp) contracted by the Ministry of Science Technology and Innovation (MCTI), however, found that phosphoethanolamine accounted for only 32.2% of the so-called "synthetic" phosphoethanolamine.…”

mentioning

confidence: 99%

Ethical issues on the "synthetic" phosphoethanolamine clinical trial

Paumgartten

2017

Rev. Assoc. Med. Bras.

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Notwithstanding its approval by the National Committee for Ethics in Research (Conep) on April 19, 2016, a trial of the so-called "synthetic" phosphoethanolamine (syn-phospho) pill in cancer patients raises ethical concerns. An analysis by a laboratory contracted by the Ministry of Science, Technology and Innovation (MCTI) revealed that syn-phospho contained a great amount of impurities and did not meet standards of pharmaceutical quality required for an investigational drug. Cytotoxicity against human tumor cell lines and in vivo rodent xenograft tumor assays consistently failed to demonstrate a potential anticancer activity of syn-phospho. Preclinical safety studies of syn-phospho were also insufficient to support a trial of this investigational drug in cancer patients. Moreover, the ethical approval decision apparently overlooked two previous findings that suggested a possible enhancement of mammary carcinoma cell proliferation by phosphoethanolamine, and an apparent increase in lung metastases (rat implanted tumor assay) by syn-phospho. The syn-phospho risk-benefit ratio is clearly unfavorable and, thus, this trial in cancer patients does not fulfill a key requirement to make a clinical research ethical. There are also concerns regarding whether the study design is robust enough (scientific validity), and the social value of the trial of syn-phospho in cancer patients is questionable.

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Preclinical Development of a Nontoxic Oral Formulation of Monoethanolamine, a Lipid Precursor, for Prostate Cancer Treatment

Saxena

Yang

Mukkavilli

et al. 2017

Clinical Cancer Research

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Purpose Most currently-available chemotherapeutic agents target rampant cell division in cancer cells, thereby affecting rapidly-dividing normal cells resulting in toxic side-effects. This non-specificity necessitates identification of novel cellular pathways that are reprogrammed selectively in cancer cells and can be exploited to develop pharmacologically superior and less-toxic therapeutics. Despite growing awareness on dysregulation of lipid metabolism in cancer cells, targeting lipid biosynthesis is still largely uncharted territory. Herein, we report development of a novel non-toxic orally-deliverable anticancer formulation of monoethanolamine (Etn), for prostate cancer by targeting the Kennedy pathway of phosphatidylethanolamine (PE) lipid biosynthesis. Experimental Design We first evaluated GI-tract stability, drug-drug interaction liability, pharmacokinetic and toxicokinetic properties of Etn to evaluate its suitability as a non-toxic orally-deliverable agent. We next performed in vitro and in vivo experiments to investigate efficacy and mechanism of action. Results Our data demonstrate that Etn exhibits excellent bioavailability, GI-tract stability, and no drug-drug interaction liability. Remarkably, orally-fed Etn inhibited tumor growth in four weeks by ~67% in mice bearing human prostate cancer PC-3 xenografts without any apparent toxicity. Mechanistically, Etn exploits selective overexpression of choline kinase in cancer cells, resulting in accumulation of phosphoethanolamine (PhosE), accompanied by downregulation of HIF-1α that induces metabolic stress culminating into cell death. Conclusions Our study provides first evidence for the superior anticancer activity of Etn, a simple lipid precursor formulation, whose non-toxicity conforms to FDA-approved standards, compelling its clinical development for prostate cancer management.

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The effect of phosphoethanolamine intake on mortality and macrophage activity in mice with solid ehrlich tumors

Abstract: ABSTRACT

Cited by 6 publications

References 22 publications

Synthetic phosphoethanolamine: the state of the art of scientific production

Synthetic phosphoethanolamine: the state of the art of scientific production

Ethical issues on the "synthetic" phosphoethanolamine clinical trial

Preclinical Development of a Nontoxic Oral Formulation of Monoethanolamine, a Lipid Precursor, for Prostate Cancer Treatment

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