Affinity of alkylphosphocholines to biological membrane of prostate cancer: studies in natural and model systems.

Anita Wnętrzak,Wojciech Kwiatek,Patrycja Dynarowicz-Łątka,Ewelina Lipiec,Kazimierz Łątka

doi:10.1007/s00232-014-9674-8

Abstract

The effectiveness of two alkylphosphocholines (APCs), hexadecylphosphocholine (miltefosine) and erucylphosphocholine to combat prostate cancer has been studied in vitro with artificial cancerous membrane, modelled with the Langmuir monolayer technique, and on cell line (Du-145). Studies performed with the Langmuir method indicate that both the investigated drugs have the affinity to the monolayer mimicking prostate cancer membrane (composed of cholesterol:POPC = 0.428) and the drug-membrane interactions are stronger for erucylphosphocholine as compared to hexadecylphosphocholine. Moreover, both studied drugs were found to fluidize the model membrane, which may lead to apoptosis. Indeed, biological studies confirmed that in Du-145 cell line both investigated alkylphosphocholines cause cell death primarily by apoptosis while necrotic cells constitute only a small percentage of APC-treated cells.

Highlights

There are plethora of studies confirming that many chemicals, including drugs, dietary supplements or environmental pollutants affect cellular membrane properties, which can further influence on cell functioning
Studies performed with the Langmuir method indicate that both the investigated drugs have the affinity to the monolayer mimicking prostate cancer membrane and the drug-membrane interactions are stronger for erucylphosphocholine as compared to hexadecylphosphocholine
Model studies carried out with the Langmuir monolayer technique unambiguously prove that both investigated APCs interact with a monolayer mimicking prostate cancer membrane

Summary

Introduction

There are plethora of studies confirming that many chemicals, including drugs, dietary supplements or environmental pollutants affect cellular membrane properties, which can further influence on cell functioning. Most frequently observed effects include changes in membrane fluidity, permittivity or membrane lipids organisation/ composition as recently reviewed by Tekpli et al (2013). Changes in membrane properties observed in vivo can be verified in model systems, which are advantageous—as compared to natural ones—of being simple and welldefined, contrary to highly variable and complex living systems. Among various membrane models applied (reviewed in Hac-Wydro and Dynarowicz-Łatka 2008; Chan and Boxer 1999), most popular are Langmuir monolayers (Hac-Wydro and Dynarowicz-Łatka 2008; Maget-Dana 1999) and liposomes/vesicles (Kell 1981). The former benefit from easiness of precise control of such model membrane parameters as its molecular packing, lateral pressure and composition

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