Phosphomonoester Phosphoethanolamine Induces Apoptosis in Human Chronic Myeloid Leukemia CellsJournal: Journal of Pharmacy and Pharmacology (Vol.7, No. 7)
Publication Date: 2019-07-07
Authors : Thais de Oliveira Conceição; Manuela Garcia Laveli da Silva; Durvanei Augusto Maria;
Page : 434-450
Keywords : ;
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+).
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