Daniela Mosiadz

Publications (4)10.87 Total impact

• Article: The Influence of Phenothiazine Derivatives on Intracellular Accumulation of Cationic Cyanine Dye DiOC6(3) in LoVo-DX Cells.

  Andrzej Pola, Daniela Mosiadz, Jolanta Saczko, Teresa Modrzycka, Krystyna Michalak
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  ABSTRACT: Aim: This study aimed to evaluate the influence of phenothiazine derivatives (PDs) on the intracellular accumulation of cyanine dye DiOC6(3) in doxorubicin-resistant LoVo-DX cell line, with overexpression of P-glycoprotein. MATERIALS AND METHODS: In order to maintain a high expression level of P-gp, the LoVo-DX cells were grown in the presence of doxorubicin (100 ng/ml). The time-dependent fluorescence signal (T-DFS) of the intracellular accumulation of DiOC6(3), in the presence of PDs, was then recorded. The rate constants k1, k2, k3 and amplitudes of T-DFS, describing the intracellular accumulation process, were determined based on the respective theoretical equation. RESULTS: The values of k1 and k2 were dependent on the hydrophobicity (logP) of the PDs used as drug resistance modulators. A rise of k1 and k2 values was observed when the logP of PDs increased. CONCLUSION: We suggest that the k1 and k2 rate constants could be regarded as useful parameters for assessment of PDs as well as of other compounds of potential application as reversers of multidrug resistance.
  Anticancer research 03/2013; 33(3):857-863. · 1.73 Impact Factor
• Article: Influence of silybin on biophysical properties of phospholipid bilayers.

  Olga Wesołowska, Barbara Łania-Pietrzak, Micha Kuzdzał, Kamila Stanczak, Daniela Mosiadz, Piotr Dobryszycki, Andrzej Ozyhar, Małgorzata Komorowska, Andrzej B Hendrich, Krystyna Michalak
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  ABSTRACT: Silybin (silibinin) is major biologically active flavonolignan extracted from milk thistle (Sylibum marianum). Its biological activities include hepato-protection, anticancer properties, and antioxidant- and membrane-stabilizing functions. Although membranes are postulated to be one of the cellular targets for silybin, little is known about its interaction with phospholipid bilayers. In the present work, the interactions of silybin with phosphatidylcholine bilayers were studied in detail using fluorescence spectroscopy, microcalorimetry and electron spin resonance techniques. The results showed that silybin interacted with the surface of lipid bilayers. It affected the generalized polarization of the fluorescent probe Prodan, while not influencing the more deeply located Laurdan. Silybin lowered the main phospholipid phase transition temperature as judged by microcalorimetry, and caused the immobilization of spin probe Tempo-palmitate located on the surface of membranes. The mobility of spin probes 5- and 16-doxyl stearic acid was not affected by silybin. Silybin-induced quenching of 1,6-diphenyl-1,3,5-hexatriene fluorescence indicated that some flavonoid molecules partitioned into the hydrophobic region of membranes, which did not change significantly the biophysical properties of the deeper membrane regions. Such a behavior of silybin in membranes is in accordance with its postulated biological functions and neglectable side effects of therapies using silybin.
  Acta Pharmacologica Sinica 03/2007; 28(2):296-306. · 1.95 Impact Factor
• Article: Phenothiazine maleates stimulate MRP1 transport activity in human erythrocytes.

  Olga Wesołowska, Daniela Mosiadz, Noboru Motohashi, Masami Kawase, Krystyna Michalak
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  ABSTRACT: The expression of multidrug resistance-associated protein (MRP1) results in ATP-dependent reduction of drugs' concentration in cancer cells, i.e., multidrug resistance (MDR). Since the majority of projects are concentrated on the search of the new MDR modulators, there are very few reports on drug-induced stimulation of MDR transporters activity. In the present work, by means of functional fluorescence assay we have shown that MRP1-mediated efflux of 2',7'-bis-(3-carboxypropyl)-5-(and-6)-carboxyfluorescein (BCPCF) out of human erythrocytes is stimulated by phenothiazine maleates that have been already identified as P-glycoprotein inhibitors. Phenothiazine maleates-induced stimulation of ATP-dependent uptake of 2',7'-bis-(3-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) into inside-out membrane vesicles prepared from erythrocyte membranes has been also demonstrated. Moreover, it was shown that phenothiazine maleates exerted stimulating effect on ATPase activity measured in erythrocyte membranes. To our best knowledge, this report is the first one demonstrating that compounds able to inhibit transport activity of P-glycoprotein can stimulate MRP1 transporter. We conclude that phenothiazine maleates probably exert their stimulatory effect on MRP1 by direct interaction with the protein at the site different from the substrate binding site.
  Biochimica et Biophysica Acta 01/2006; 1720(1-2):52-8. · 4.66 Impact Factor
• Article: Modulation of MRP1 protein transport by plant, and synthetically modified flavonoids.

  Barbara Łania-Pietrzak, Krystyna Michalak, Andrzej B Hendrich, Daniela Mosiadz, Grzegorz Grynkiewicz, Noboru Motohashi, Yoshiaki Shirataki
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  ABSTRACT: The influence of novel synthetic and plant origin flavonoids on activity of multidrug resistance-associated protein (MRP1) was investigated in human erythrocytes used as a cell model expressing MRP1 in plasma membrane. The fluorescent probe, BCPCF (2', 7'-bis-(3-carboxy-propyl)-5-(and-6)-carboxyfluorescein), was applied as a substrate for MRP1 multidrug resistance transporter. The effect of compounds belonging to different classes of natural flavonoids: flavone, flavonol, isoflavones and flavanolignan was compared with action of new synthetic derivatives of genistein. Most of the flavonoids showed strong or moderate ability to inhibit transport carried out by MRP1. Inhibitory properties of flavonoids were compared to the effects of indomethacin, probenecid and MK-571 known as MRP1 inhibitors. Studying the influence of new synthetic genistein derivatives on BCPCF transport we have found that the presence of hydrophobic groups substituting hydrogen of hydroxyl group at the position 4' in ring B of isoflavone is more important for inhibitory properties than hydrophobic substitution at the position 7 in ring A. In case of naturally occurring isoflavones the replacement of hydrogen at position 4' by hydrophobic ring structure seems also to be favourable for inhibition potency.
  Life Sciences 09/2005; 77(15):1879-91. · 2.53 Impact Factor