ANTİNEOPLASTİK AJAN-MODEL MEMBRAN ETKİLEŞİMLERİNİN BİYOFİZİKSEL AÇIDAN MOLEKÜLER DÜZEYDE İNCELENMESİ
Project no. 20901 · Status: Kapanmış · 2019
Summary
<p>Miltefosine (MLT) is a broad-spectrum drug included in the group of alkylphospholipids (APL) used against leishmania and various types of cancer. It is thought that the most important feature of APLs is that they only kill cancerous cells without harming normal cells. However, the action mechanism of APLs at the molecular level is not yet known in detail. This study aimed to elucidate the action mechanisms of MLT at the molecular level on normal and cancer cell membranes as well as the status of increasing the ratio of PS in the membrane, which is a marker showing the stage of cancer and even metastasis. The interaction of MLT with multilayered liposomes (MLVs) of dipalmitoyl phosphatidylcholine (DPPC) mimicking healthy cell membrane, dipalmitoyl phosphatidylserine (DPPS) mimicking cancer cell membrane and also DPPC/DPPS(3:1) and DPPC/DPPS (1:1) liposomes mimicking membrane structures where increased DPPS ratio in the structure is associated with early stage of cancer or metastasis status, the effects on membrane phase transition, membrane order and membrane dynamics were investigated depending on temperature and concentration using Fourier Transform Infrared (FTIR) spectroscopy and Differential Scanning Calorimetry (DSC). Comparative results show that MLT affects DPPS/MLT systems mimicking cancer cells more than DPPC/MLT systems mimicking healthy cells, and the interaction increases as the DPPS ratio increases in the structure. Our results show that miltefosine is the evidence at the molecular level that it is directed towards the tumor cell, and that the effect of the drug increases with the increase of anionic lipids in the membrane depending on the stage of the cancer.</p>