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1

Interaction of phenothiazines, stilbenes and flavonoids with multidrug resistance-associated transporters, P-glycoprotein and MRP1

100%

Wesołowska O.

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2011

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vol. 58

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issue 4

433-448

EN

Multidrug resistance (MDR) of cancer cells poses a serious obstacle to successful chemotherapy. The overexpression of multispecific ATP-binding cassette transporters appears to be the main mechanism of MDR. A search for MDR-reversing agents able to sensitize resistant cells to chemotherapy is ongoing in the hope of their possible clinical use. Studies of MDR modulators, although they have not produced clinically beneficial effects yet, may greatly enrich our knowledge about MDR transporters, their specificity and mechanism of action, especially substrate and/or inhibitor recognition. In the present review, interactions of three groups of modulators: phenothiazines, flavonoids and stilbenes with both P-glycoprotein and MRP1 are discussed. Each group of compounds is likely to interact with the MDR transporters by a different mechanism. Phenothiazines probably interact with drug binding sites, but they also could indirectly affect the transporter's activity by perturbing lipid bilayers. Flavonoids mainly interact with ABC proteins within their nucleotide-binding domains, though the more hydrophobic flavonoids may bind to regions within transmembrane domains. The possible mechanism of MDR reversal by stilbenes may result from their direct interaction with the transporter (possibly within substrate recognition sites) but some indirect effects such as stilbene-induced changes in gene expression pattern and in apoptotic pathways should also be considered. Literature data as well as some of our recent results are discussed. Special emphasis is put on cases when the interactions of a given compound with both P-glycoprotein and MRP1 have been studied simultaneously.

2

Giant unilamellar vesicles - a perfect tool to visualize phase separation and lipid rafts in model systems

51%

Wesołowska O., Michalak K., Maniewska J., Hendrich A. B.

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issue 1

33-39

EN

Model systems such as black lipid membranes or conventional uni- or multilamellar liposomes are commonly used to study membrane properties and structure. However, the construction and dimensions of these models excluded their direct optical microscopic observation. Since the introduction of the simple method of liposome electroformation in alternating electric field giant unilamellar vesicles (GUVs) have become an important model imitating biological membranes. Due to the average diameter of GUVs reaching up to 100 µm, they can be easily observed under a fluorescent or confocal microscope provided that the appropriate fluorescent probe was incorporated into the lipid phase during vesicle formation. GUVs can be formed from different lipid mixtures and they are stable in a wide range of physical conditions such as pH, pressure or temperature. This mini-review presents information about the methods of GUV production and their usage. Particularly, the use of GUVs in studying lipid phase separation and the appearance and behavior of lipid domains (rafts) in membranes is discussed but also other examples of GUVs use in membrane research are given. The experience of the authors in setting up the GUV-forming equipment and production of GUVs is also presented.

3

Phage display of proteins

39%

Kościelska K., Kiczak L., Kasztura M., Wesołowska O., Otlewski J.

Acta Biochimica Polonica

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1998

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vol. 45

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issue 3

705-720

Refine search results

3 Acta Biochimica Polonica

1 2011

1 2009

1 1998

3 Wesołowska O.

1 Hendrich A. B.

1 Kasztura M.

1 Kiczak L.

1 Kościelska K.

1 Maniewska J.

1 Michalak K.

1 Otlewski J.

Interaction of phenothiazines, stilbenes and flavonoids with multidrug resistance-associated transporters, P-glycoprotein and MRP1

Giant unilamellar vesicles - a perfect tool to visualize phase separation and lipid rafts in model systems

Phage display of proteins