Synthetic phosphoethanolamine a precursor of membrane phospholipids reduce tumor growth in mice bearing melanoma B16-F10 and in vitro induce apoptosis and arrest in G2/M phase

Ferreira, Adilson Kleber; Meneguelo, Renato; Marques, Fábio Luiz Navarro; Radin, A; Filho, Otaviano Mendonça Ribeiro; Neto, Salvador Claro; Chierice, Gilberto Orivaldo; Maria, Durvanei Augusto

doi:10.1016/j.biopha.2012.04.008

Cited by 30 publications

(70 citation statements)

References 16 publications

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“…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.…”

Section: Methodsmentioning

confidence: 99%

“…2,3 In a recent report, we showed that synthetic phosphoethanolamine (PHO-S), an aminoethyl phosphoric ester, has a great potential to induce cell death in B16F10 (melanoma murine) cells and without apparent damage to normal cells, such as fibroblasts and lymphocytes. 4,5 We demonstrated that PHO-S is effective in the reduction of DNA…”

Section: Introductionmentioning

confidence: 97%

“…5 It caused a decrease in cyclin D1 mRNA, VEGFR1 gene transcription, and VEGFR1 receptor expression. In vitro antiangiogenic activity assays showed that PHO-S inhibits endothelial cell proliferation, migration, and tube formation.…”

mentioning

confidence: 99%

“…[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.…”

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confidence: 99%

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Potential antitumor activity of novel DODAC/PHO-S liposomes

Luna

Saraiva²,

Filho³

et al. 2016

IJN

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In recent studies, we showed that synthetic phosphoethanolamine (PHO-S) has a great potential for inducing cell death in several tumor cell lines without damage to normal cells. However, its cytotoxic effect and selectivity against tumor cells could increase with encapsulation in cationic liposomes, such as dioctadecyldimethylammonium chloride (DODAC), due to electrostatic interactions between these liposomes and tumor cell membranes. Our aim was to use cationic liposomes to deliver PHO-S and to furthermore maximize the therapeutic effect of this compound. DODAC liposomes containing PHO-S (DODAC/PHO-S), at concentrations of 0.3–2.0 mM, prepared by ultrasonication, were analyzed by scanning electron microscopy (SEM) and dynamic light scattering. The cytotoxic effect of DODAC/PHO-S on B16F10 cells, Hepa1c1c7 cells, and human umbilical vein endothelial cells (HUVECs) was assessed by MTT assay. Cell cycle phases of B16F10 cells were analyzed by flow cytometry and the morphological changes by SEM, after treatment. The liposomes were spherical and polydisperse in solution. The liposomes were stable, presenting an average of ∼50% of PHO-S encapsulation, with a small reduction after 40 days. DODAC demonstrated efficient PHO-S delivery, with the lowest values of IC 50% (concentration that inhibits 50% of the growth of cells) for tumor cells, compared with PHO-S alone, with an IC 50% value of 0.8 mM for B16F10 cells and 0.2 mM for Hepa1c1c7 cells, and without significant effects on endothelial cells. The Hepa1c1c7 cells showed greater sensitivity to the DODAC/PHO-S formulation when compared to B16F10 cells and HUVECs. The use of DODAC/PHO-S on B16F10 cells induced G 2 /M-phase cell cycle arrest, with the proportion significantly greater than that treated with PHO-S alone. The morphological analysis of B16F10 cells by SEM showed changes such as “bleb” formation, cell detachment, cytoplasmic retraction, and apoptotic bodies after DODAC/PHO-S treatment. Cationic liposomal formulation for PHO-S delivery promoted cytotoxicity more selectively and effectively against B16F10 and Hepa1c1c7 cells. Thus, the DODAC/PHO-S liposomal formulation presents great potential for preclinical studies.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Potential antitumor activity of novel DODAC/PHO-S liposomes

Luna

Saraiva²,

Filho³

et al. 2016

IJN

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“…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.…”

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confidence: 99%

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

Rêgo

Lopes

Riechelmann

et al. 2017

Rev. Assoc. Med. Bras.

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Local tumour response to neoadjuvant therapy with 2‐aminoethyl dihydrogen phosphate in dogs with soft tissue sarcoma

Castro

Maria

Pinto

et al. 2022

Veterinary Medicine & Sci

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Background In cases of soft tissue sarcoma (STS), neoadjuvant therapy is indicated to downstage the tumour prior to surgery to achieve enhanced local tumour control. The antineoplastic phospholipid compound 2‐aminoethyl dihydrogen phosphate (2‐AEH2F) is an alkyl phosphate ester capable of inhibiting cell proliferation and inducing cell death by modifying the asymmetry of phospholipids in the cytoplasmic membrane Objectives This clinical study was designed to investigate local antitumoural effects of neoadjuvant therapy with 2‐AEH2F in dogs with naturally occurring STS Material and methods Dogs (n = 11) received four consecutive weekly intravenous injections of 2‐AEH2F (70 mg/kg) prior to tumour resection. Tomographic (CT) and thermal (TE) images were used to investigate changes in tumour size and local temperature in response to treatment Results Comparative analysis of CT images (n = 9/11) failed to reveal complete or partial remission according to selected assessment criteria (RECIST, WHO and volumetric). Comparative analysis of TE images (n = 10/11) revealed significantly (p = 0.01416) lower temperatures in tumoural areas relative to surrounding tissues over the course of treatment Conclusions 2‐AEH2F had no cytoreductive effects when used at doses and intervals described in this study. However, significant drop in skin temperatures recorded in tumoural areas suggest induction of physiological changes.

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Synthetic phosphoethanolamine a precursor of membrane phospholipids reduce tumor growth in mice bearing melanoma B16-F10 and in vitro induce apoptosis and arrest in G2/M phase

Cited by 30 publications

References 16 publications

Potential antitumor activity of novel DODAC/PHO-S liposomes

Potential antitumor activity of novel DODAC/PHO-S liposomes

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

Local tumour response to neoadjuvant therapy with 2‐aminoethyl dihydrogen phosphate in dogs with soft tissue sarcoma

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