New potential antiproliferative monophosphoester 2-aminoethyl dihydrogen phosphate in K-562 and K-562 MDR+ leukemia cells.

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+).

• Authors: T O Conceição, Lgs Cabral, M G Laveli-Silva, J C Pacheco, M G Alves, D C Rabelo, Ran Laiso, D A Maria
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 142 Pg. 112054 (Oct 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34463267 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier Masson SAS.

Chemical References

• 2-aminoethyl phosphate
• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• Liposomes
• Oleic Acids
• Organophosphates
• Quaternary Ammonium Compounds
• dioleyldimethylammonium chloride

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Cell Cycle (drug effects)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Drug Resistance, Multiple (drug effects)
• Drug Synergism
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, pathology)
• Liposomes (chemistry, pharmacology)
• Membrane Potential, Mitochondrial (drug effects)
• Oleic Acids (chemistry, pharmacology)
• Organophosphates (pharmacology)
• Quaternary Ammonium Compounds (chemistry, pharmacology)