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

Biomed Pharmacother. 2021 Oct:142:112054. doi: 10.1016/j.biopha.2021.112054. Epub 2021 Aug 27.

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+).

Keywords: 2-AEH(2)P; DODAC carrier; Drug resistance; Leukemia; Liposomal formulation.

MeSH terms

  • 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*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Liposomes / chemistry
  • Liposomes / pharmacology
  • Membrane Potential, Mitochondrial / drug effects
  • Oleic Acids / chemistry
  • Oleic Acids / pharmacology
  • Organophosphates / pharmacology*
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / pharmacology

Substances

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