In vitro effects of the antitumor drug miltefosine on human erythrocytes and molecular models of its membrane

Karla Petit, Mario Suwalsky, José R. Colina, LUIS FELIPE AGUILAR CAVALLO, Malgorzata Jemiola-Rzeminska, Kazimierz Strzalka

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

This study was aimed at elucidating the molecular mechanisms of the interaction of the antitumor alkylphospholipid drug miltefosine with human erythrocytes (RBC) and molecular models of its membrane. The latter consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. X-ray results showed that the drug interacted with DMPC multilayers; however, no effects on DMPE were detected. The experimental findings obtained by differential scanning calorimetry (DSC) indicated that miltefosine altered the thermotropic behavior of both DMPC and DMPE vesicles. Fluorescence spectroscopy evidenced an increase in the fluidity of DMPC vesicles and human erythrocyte membranes. Scanning electron microscopy (SEM) observations on human erythrocytes showed that miltefosine induced morphological alterations to RBC from its normal biconcave to an echinocyte type of shape. These results confirm that miltefosine interacts with the outer moiety of the human erythrocyte membrane affecting the cell morphology.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1861
Issue number1
DOIs
StatePublished - Jan 2019
Externally publishedYes

Keywords

  • Antitumor
  • Erythrocyte
  • Miltefosine
  • Phospholipid bilayer

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