Phosphomonoester Phosphoethanolamine Induces Apoptosis in Human Chronic Myeloid Leukemia Cells

Abstract

Background: Leukemia is a type of cancer that starts in the blood or blood-forming tissues.It results from the clonal proliferation of hematopoietic cells in the bone marrow and/or lymphoid tissues, which subsequently reach the peripheral circulation and can infiltrate other systems.There are many different kinds of leukemia, and treatments are different for each one.Chronic leukemia is with a slower growing than acute leukemia but could be just as life-threatening.Phospholipids are antitumor analogs, such as synthetic phosphoethanolamine, which is a phosphorylated compound capable of controlling cellular proliferation and inducing apoptosis in several types of tumor cells.Methods: K562 and K562-Lucena (MDR+) human chronic myeloid leukemia cells were treated with synthetic phosphoethanolamine (Pho-s).The viability was evaluated by sulforhodamine B (SRB) assay and cell cycle phases, apoptosis, markers expression, and mitochondrial potential were assessed by flow cytometry.Results: Tumor cells formed clusters in suspension and decreased significantly viability.The concentrations for IC50% were obtained.Pho-s treated were 43.1 mM (K562) and 145.9 mM (K562-Lucena MDR+) in a period of 24 hours.Pho-s induced changes in the distribution of cell population phases of cell cycle which showed an increase in fragmented DNA and increased markers expression envolved apoptosis pathways a decrease in the G1/G0 phase.Discussion: Treatment of K562 and K562-Lucena (MDR+) chronic myeloid leukemia cells with Pho-s showed dose and time dependent cytotoxic effects.This cytotoxicity induced a decrease in proliferative capacity, mitochondrial electrical potential, and consequently release of cytochrome C; inhibition of Bcl-2 family protein expression, increase in pro-apoptotic family members Bad and Bax, dependent on p53 expression.Conclusion: This study presented a significant therapeutic potential of Phos-s in this type of leukemia through the apoptotic effects on tumor cells independently of the molecular resistance profile (MDR+).