New potential antiproliferative monophosphoester 2-aminoethyl dihydrogen phosphate in K-562 and K-562 MDR+ leukemia cells - 18/09/21
, LGS. Cabral a, b, 1 , MG. Laveli-Silva a, b, JC. Pacheco a, b, MG. Alves a, b, DC. Rabelo a, RAN. Laiso b, DA. Maria a, b, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Abstract |
The main obstacle in the treatment of cancer patients has been resistance to multiple drugs, leading to the need to develop molecules with a higher specificity target. The liposomal formulation DODAC/2-AEH2P has antitumor potential, inducing apoptosis in several tumor types. Human chronic myeloid leukemia K-562 and K-562 Lucena (MDR+) cells were treated with the DODAC carrier and the liposomal formulation 2-AEH2P. Viability, cell cycle phases, apoptosis, marker expression and mitochondrial potential were analyzed. Significant reduction in viability was observed for all treatments. Changes in the distribution of the cell cycle phases and expression of markers involved in the apoptosis pathways were observed. Reduction of the mitochondrial electrical potential mediated by Bcl-2, being regulated by the reduction of the MTCH2 protein linked to the progression of myeloid leukemia and an increase in the pro-apoptotic proteins Bad and Bax, dependent on p53. This study demonstrated a significant therapeutic potential through apoptotic effects in leukemic cells, regardless of the molecular resistance profile (MDR+).
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Highlights |
• | The liposomal formulation with 2-AEH2P induce response antiproliferative in human chronic myeloid leukemia K-562 and K-562 Lucena (MDR+) cells. |
• | The potent synergistic effect was observed for K-562 leukemia cells, while in K-562 Lucena (MDR+) resistant cells, the liposomal formulation 2-AEH2P showed an additive pharmacological effect. |
• | The increase in the expression of regulatory proteins p21 and p27 suggests the antiproliferative potential of liposomal formulation 2-AEH2P with ability to interfere with the progression and regulation of the cell cycle. |
Keywords : Leukemia, Drug resistance, DODAC carrier, Liposomal formulation, 2-AEH2P
Plan
Vol 142
Article 112054- octobre 2021 Retour au numéro
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