Avaliação do potencial antileucêmico de adutos aromáticos de morita-baylis-hillman.
Leukemia includes a variety of hematological carcinogenic diseases, affecting various cell types at different stages of cellular maturation. This pathology can be classified in four classes: acute and chronic, which are divided into lymphoid and myeloid. A nti - leukemic drugs have been important tools in the treatment of this disease; however these substances have been displayed problems, showed a low selectivity and high toxicity, which have limited their use in the clinical treatment. Therefore, aim of this study was to investigate the cytotoxicity of some substances classified as Morita - Baylis - Hillman adducts (MBHA), using the culture of some leukemic cells, HL - 60, K562, K562 - Lucena and MOLT - 4, as well as normal cells from peripheral blood mononuclear cell (PBMC). The effect of these MBHA synthetic molecules were evaluated by MTT reduction and neutral red uptake techniques and the mechanism of cell death was studied using differential staining tests with acridine orange and ethidium bromide (LA/BE) probes, b eing observed under fluorescence microscope. The cell cycle and mitochondrial transmembrane potential analyzes were measured using the flow cytometry technique. Using the MTT assay, the compound A2CN showed greater potency against the strain HL - 60 (IC 50 = 22 μM) and MOLT - 4 (21 μM ) than in PBMC (71 μM) after 24 hours of incubation. In the resistant K562 cells, the A2CN showed an IC 50 of 58 μM, and for K562 - Lucena cells the IC 50 w as 60 μM. In studies of cell death, the A2CN induced an increase of apoptotic c ells assessed by fluorescence microscopy. In addition A2CN induced DNA fragmentation and depolarization of the mitochondrial membrane; both results were assessed by flow cytometry. It was concluded that the substance A2CN induced apoptosis in leukemia cell s with higher selectivity for leukemic lineage than for the non - tumor cells.
Adutos de morita-baylis-hillman, Apoptose, Citotoxicidade, Leucemia
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