Issue 1, 2016

Effect of lipid peroxidation on membrane permeability of cancer and normal cells subjected to oxidative stress

Abstract

We performed molecular dynamics simulations to investigate the effect of lipid peroxidation products on the structural and dynamic properties of the cell membrane. Our simulations predict that the lipid order in a phospholipid bilayer, as a model system for the cell membrane, decreases upon addition of lipid peroxidation products. Eventually, when all phospholipids are oxidized, pore formation can occur. This will allow reactive species, such as reactive oxygen and nitrogen species (RONS), to enter the cell and cause oxidative damage to intracellular macromolecules, such as DNA or proteins. On the other hand, upon increasing the cholesterol fraction of lipid bilayers, the cell membrane order increases, eventually reaching a certain threshold, from which cholesterol is able to protect the membrane against pore formation. This finding is crucial for cancer treatment by plasma technology, producing a large number of RONS, as well as for other cancer treatment methods that cause an increase in the concentration of extracellular RONS. Indeed, cancer cells contain less cholesterol than their healthy counterparts. Thus, they will be more vulnerable to the consequences of lipid peroxidation, eventually enabling the penetration of RONS into the interior of the cell, giving rise to oxidative stress, inducing pro-apoptotic factors. This provides, for the first time, molecular level insight why plasma can selectively treat cancer cells, while leaving their healthy counterparts undamaged, as is indeed experimentally demonstrated.

Graphical abstract: Effect of lipid peroxidation on membrane permeability of cancer and normal cells subjected to oxidative stress

Supplementary files

Article information

Article type
Edge Article
Submitted
25 Jun 2015
Accepted
14 Oct 2015
First published
16 Oct 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 489-498

Author version available

Effect of lipid peroxidation on membrane permeability of cancer and normal cells subjected to oxidative stress

J. Van der Paal, E. C. Neyts, C. C. W. Verlackt and A. Bogaerts, Chem. Sci., 2016, 7, 489 DOI: 10.1039/C5SC02311D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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