2-aminoethyl Dihydrogen Phosphate as a Modulator of Proliferative and Apoptotic Effects in Breast Cancer Cell Lines

Background: Breast cancer is a type of cancer that affects more women throughout the world, in developing anddeveloped countries. 2-AEH2P is a phospholipid analog of cellular membrane, which makes it different from existing molecules fortheir absorption, stability and display anti-inflammatory, anti-proliferative and pro-apoptotic properties. Methods: MCF-7 humanbreast adenocarcinoma cells were treated with 2-AEH2P. The viability and adhesion cells were evaluated by MTT assay. Cell cyclephases, apoptosis, markers and mitochondrial potential were assessed by flow cytometry. Morphological ultrastructural analyzeswere performed by laser confocal microscopy. Results: MCF-7 Tumor cells acquired round shapes, lost cytoplasmic expansions,formed clusters in suspension and decreased significantly viability. There were changes in the morphology, membrane fragmentationand loss of cytoplasmic projection. The obtained concentrations for IC50% were 37.2;25.8;1.8 mM for periods of 24, 48 and 72 h,respectively. Changes in the distribution of cell population phases of the cell cycle showed an increase in fragmented DNA and anincrease in the G2/M phase. The expression β-gal showed proliferative reduction induced by 2-AEH2P. Laser confocal microscopyshowed changes in the mitochondrial membrane and alteration in distribution. Proliferative index of MCF-7 tumor cells treated with2-AEH2P decreased significantly when compared to fibroblast normal cells. The compound 2-AEH2P is a phospholipid withantiproliferative potential and apoptosis modulator.

Clinical Oncology Translational Study Phase-1 with Antitumor Phosphorylethanolamine(2-AEH_(2)P)in Dogs with Neoplasms

The animal has the potential to serve as a clinical model for human disease,due to striking similarities and homologies in diseases.Early clinical development of a new drug may influence its final destination,and a careful and thoughtful approach to Phase-1 clinical trials is essential.Phosphorylethanolamine(2-AEH2P)is a new cytostatic phospholipid agent that,unlike most chemotherapeutic drugs used today,does not target DNA or cytoskeleton,but act on the cell membrane.Studies carried out by our group have shown several effects of 2-AEH2P controlling the progression of the cell cycle,in the alterations of the mitochondrial electrical potential capable of inducing apoptosis and autophagy in several types of human and animal tumor cells.The aim of this study is to establish the recommended safety dose of a 2-AEH2P monophosphoester,in dogs with tumor following the Phase 1 study model proposed by Fibonacci.The Phase-1 study following the Fibonacci model,2-AEH2P was safe at all staggered doses up to 150 mg/Kg for 8 weeks.Intravenous administration in staggered doses according to the Fibonacci model,showed that the drug is safe,no advent of mortality during the study period or acute toxicity were observed.It is not a drug with hemolytic properties or that induces anemia.It does not lead to changes in liver and renal functions and was able to modulate leukocyte production.2-AEH2P is new compound with antitumor potential,being useful for future veterinary and human tumors,as a combination of chemotherapeutic agents.