Interaction of the Anticancer Drug Tamoxifen with the Human Erythrocyte Membrane and Molecular Models

1998 ◽  
Vol 53 (3-4) ◽  
pp. 182-190 ◽  
Author(s):  
M. Suwalsky ◽  
P. Hernández ◽  
F. Villena ◽  
F. Aguilar ◽  
C. P. Sotomayor
Keyword(s):  
Erythrocyte Membrane ◽  
Anticancer Drug ◽  
Acyl Chain ◽  
Human Erythrocytes ◽  
Phospholipid Bilayer ◽  
Molecular Models ◽  
X Ray Diffraction ◽  
Human Erythrocyte Membrane ◽  
X Ray ◽  
Bilayer Couple

Abstract Tamoxifen, Anticancer Drug, Erythrocyte Membrane, Phospholipid Bilayer Tamoxifen is a non steroidal antiestrogen drug extensively used in the prevention and treatment of hormone-dependent breast cancer. To evaluate its perturbing effect upon cell membranes it was made to interact with human erythrocytes and molecular models. These consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and of dimyristoylphospha-tidylethanolamine (DMPE), representative of phospholipids classes located in the outer and inner leaflets of the erythrocyte membrane, respectively. Experiments by fluorescence spectroscopy showed that tamoxifen interacted with DMPC vesicles fluidizing both its polar head and acyl chain regions. These results were confirmed by X-ray diffraction which indi­ cated that tamoxifen perturbed the same regions of the lipid. However, it did not cause any significant structural perturbation to DMPE bilayers. The examination by electron micro­ scopy of human erythrocytes incubated with tamoxifen revealed that they changed their normal discoid shape to stomatocytes. According to the bilayer couple hypothesis, this result means that the drug is inserted in the inner leaflet of the erythrocyte membrane. Given the fact that tamoxifen did not interact with DMPE, it is concluded that it interacted with a protein located in the cytoplasmic moiety of the erythrocyte membrane.

The Anticancer Drug Adriamycin Interacts with the Human Erythrocyte Membrane

1999 ◽  
Vol 54 (3-4) ◽  
pp. 271-277 ◽  
Author(s):  
Mario Suwalsky ◽  
Pedro Hernández ◽  
Fernando Villena ◽  
Felipe Aguilar ◽  
Carlos P. Sotomayor
Keyword(s):  
Erythrocyte Membrane ◽  
Anticancer Drug ◽  
Acyl Chain ◽  
Phospholipid Bilayer ◽  
X Ray Diffraction ◽  
Human Erythrocyte Membrane ◽  
X Ray ◽  
Hydrophobic Moiety ◽  
Large Unilamellar Vesicles ◽  
Membrane Binding Sites

Abstract Adriamycin, Anticancer Drug, Erythrocyte Membrane, Phospholipid Bilayer Adriamycin is an aminoglycosidic anthracycline antibiotic widely used in the treatment of cancer. Increasing reports point to the involvement of cell membranes in its mechanism of action. The interaction of adriamycin with human erythrocytes was investigated in order to determine the membrane binding sites and the resultant structural perturbation. Electron microscopy revealed that red cells incubated with the therapeutical concentration of the drug in human plasma changed their discoid shape to both stomatocytes and echinocytes. Accord­ing to the bilayer couple hypothesis, this means that adriamycin was incorporated into either the inner or outer leaflets of the erythrocyte membrane. To explain this unusual result, the drug was incubated with molecular models. One of them consisted of dimyristoylphosphati-dylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) multilayers, representative of phospholipid classes located in the outer and inner leaflets of the erythrocyte membrane, respectively. X-ray diffraction showed that adriamycin interaction perturbed the polar head and acyl chain regions of both lipids. Fluorescence spectroscopy on another model, consisting of DMPC large unilamellar vesicles (LUV), confirmed the X-ray results in that adriamycin fluidized its hydrophobic moiety. It is concluded that adriamycin incorporates into both erythrocyte leaflets affecting its membrane structure.

The Anticancer Drug Cisplatin Interacts with the Human Erythrocyte Membrane

2000 ◽  
Vol 55 (5-6) ◽  
pp. 461-466 ◽  
Author(s):  
Mario Suwalsky ◽  
Pedro Hernández ◽  
Fernando Villena ◽  
Carlos P. Sotomayor
Keyword(s):  
Erythrocyte Membrane ◽  
Human Erythrocyte ◽  
Model Systems ◽  
X Ray Diffraction ◽  
Human Erythrocyte Membrane ◽  
X Ray ◽  
Phospholipid Classes ◽  
Functional Membrane ◽  
Dmpc Bilayer ◽  
Outer Monolayer

Drugs which exert their effects by interacting with DNA cause structural and functional membrane alterations which may be essential for growth inhibition by these agents. This paper describes the interaction of cisplatin with the human erythrocyte membrane and models constituted by bilayers of dimyristoylphosphatidylethanolamine (DMPE) and diacylphosphatidylserine (DAPS), representative of phospholipid classes located in the inner monolayer of the erythrocyte membrane, and of dimyristoylphosphatidylcholine (DMPC), a class present in its outer monolayer. Cisplatin ability to perturb DMPE, DAPS and DMPC bilayer structures was determined by X-ray diffraction and fluorescence spectroscopy. Electron microscopy disclosed that human erythrocytes incubated with 35 μм cisplatin, which is its therapeutical concentration in serum, developed cup-shaped forms (stomatocytes). According to the bilayer couple hypothesis, this means that the drug is inserted into the inner monolayer of the erythrocyte membrane, a conclusion supported by the studies on model systems.

Waveguide-enhanced scattering from thin biomolecular films

2002 ◽  
Vol 35 (2) ◽  
pp. 163-167 ◽  
Author(s):  
F. Pfeiffer ◽  
U. Mennicke ◽  
T. Salditt
Keyword(s):  
Lipid Bilayers ◽  
Signal To Noise Ratio ◽  
Acyl Chain ◽  
Grazing Incidence ◽  
Waveguide Structure ◽  
X Ray Diffraction ◽  
Signal To Noise ◽  
X Ray ◽  
Grazing Incidence Diffraction ◽  
Chain Ordering

An X-ray diffraction experiment on multilamellar membranes incorporated into an X-ray waveguide structure is reported. In the device, the lipid bilayers are confined to one side by the silicon substrate and to the other side by an evaporated thin metal cap layer. Shining a highly brilliant X-ray beam onto the system, resonantly enhanced, precisely defined and clearly distinguishable standing-wavefield distributions (modes) are excited. The in-plane structure of the acyl chain ordering is then studied by grazing incidence diffraction under simultaneously excited modes. A significant gain in signal-to-noise ratio as well as enhanced spatial resolution can be obtained with such a setup.

Effects of lithium on the human erythrocyte membrane and molecular models

2007 ◽  
Vol 129 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Mario Suwalsky ◽  
Paulo Fierro ◽  
Fernando Villena ◽  
Carlos P. Sotomayor
Keyword(s):  
Erythrocyte Membrane ◽  
Human Erythrocyte ◽  
Molecular Models ◽  
Human Erythrocyte Membrane

Comparative X-Ray Studies on the Interaction of Carotenoids with a Model Phosphatidylcholine Membrane

2002 ◽  
Vol 57 (1-2) ◽  
pp. 129-134 ◽  
Author(s):  
Mario Faculty of Chemical Sciences, Unive ◽  
Paulina Hidalgo ◽  
Kazimierz Strzalka ◽  
Anna Kostecka-Gugala
Keyword(s):  
Structural Damage ◽  
Molecular Model ◽  
Acyl Chain ◽  
Aqueous Media ◽  
Molecular Characteristics ◽  
Hydrophobic Core ◽  
X Ray Diffraction ◽  
X Ray ◽  
Epoxy Groups ◽  
Β Carotene

The interaction of structurally different carotenoids with a membrane molecular model was examined by X-ray diffraction. The selected compounds were β-carotene, lycopene, lutein, violaxanthin, zeaxanthin, and additionally carotane, a fully saturated derivative of β-carotene. They present similarities and differences in their rigidity, the presence of terminal ionone rings and hydroxy and epoxy groups bound to the rings. The membrane models were multibilayers of dipalmitoylphosphatidylcholine (DPPC), chosen for this investigation because the 3 nm thickness of the hydrophobic core of its bilayer coincides with the thickness of the hydrophobic core of thylakoid membranes and the length of the carotenoid molecules. Results indicate that the six compounds induced different types and degrees of structural perturbations to DPPC bilayers in aqueous media. They were interpreted in terms of the molecular characteristics of DPPC and the carotenoids. Lycopene and violaxanthin induced the highest structural damage to the acyl chain and polar headgroup regions of DPPC bilayers, respectively.

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