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. 2024 Aug;56(4):461-473.
doi: 10.1007/s10863-024-10025-y. Epub 2024 Jun 4.

Investigation of miltefosine-model membranes interactions at the molecular level for two different PS levels modeling cancer cells

Züleyha Özçelik Çetinel  1 , Duygu Bilge  2
Affiliations

Investigation of miltefosine-model membranes interactions at the molecular level for two different PS levels modeling cancer cells

Züleyha Özçelik Çetinel et al. J Bioenerg Biomembr. 2024 Aug.

Abstract

Miltefosine (MLT) is a broad-spectrum drug included in the alkylphospholipids (APL) used against leishmania and various types of cancer. The most crucial feature of APLs is that they are thought to only kill cancerous cells without harming normal cells. However, the molecular mechanism of action of APLs is not completely understood. The increase in the phosphatidylserine (PS) ratio is a marker showing the stage of cancer and even metastasis. The goal of this research was to investigate the molecular effects of miltefosine at the molecular level in different PS ratios. The effects of MLT on membrane phase transition, membrane orders, and dynamics were studied using DPPC/DPPS (3:1) and DPPC/DPPS (1:1) multilayer (MLV) vesicles mimicking DPPS ratio variation, Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared spectroscopy (FTIR). Our findings indicate that miltefosine is evidence at the molecular level that it is directed towards the tumor cell and that the drug's effect increases with the increase of anionic lipids in the membrane depending on the stage of cancer.

Keywords: Cancer; Differential scanning calorimetry; Dipalmitoyl phosphatidylserine level; Fourier transformation infrared spectroscopy; Miltefosine.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
DSC thermograms of DPPC/DPPS(3:1)/MLT (a) and DPPC/DPPS(1:1)/MLT (b) systems with different mol% miltefosine
Fig. 2
Fig. 2
Deconvolution analyzes of (a) DPPC/DPPS(3:1)/MLT and (b) DPPC/DPPS(1:1)/MLT systems containing different mol% miltefosine
Fig. 3
Fig. 3
a, b, c, d illustrates the change in the vibrational bands of the DPPC/DPPS(3:1) liposomes’ head, interfacial region, and tail containing 3 and 6 mol% miltefosine concentrations
Fig. 4
Fig. 4
a, b, c, d shows the change in the vibrational bands of the DPPC/DPPS(1:1) liposomes’ head, interfacial region, and tail containing 3 and 6 mol% MLT concentrations
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