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Comparative effects of selected plant polyphenols, gallic acid and epigallocatechin gallate, on matrix metalloproteinases activity in multidrug resistant MCF7/DOX breast cancer cells

100%
Nowakowska A., Tarasiuk J.
Acta Biochimica Polonica
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2016
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vol. 63
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issue 3
571-575
EN
The aim of the study was to investigate the effect of selected polyphenols: gallic acid (GA) and epigallocatechin gallate (EGCG) on matrix metalloproteinase (MMP-2 and MMP-9) activity in multidrug resistant (MDR) human breast adenocarcinoma cells: MCF7/DOX cells and obtained recently in our laboratory MCF7/DOX500 cells by the permanent selection of MCF7/DOX cells with 500 nM doxorubicin (DOX). The activity of MMP-2 and MMP-9 and the effect of studied polyphenols on these matrix proteases were examined by gelatin zymography assays. We have found that the activity of MMP-2 and MMP-9 significantly increased in resistant MCF7/DOX and MCF7/DOX500 cells whereas they were not detected in sensitive MCF7 cells. It was also observed that GA (30, 60, 100 and 120 µM) and EGCG (5, 10 and 20 µM) caused a comparable concentration-dependent inhibition of MMP-2 and MMP-9 activity in MCF7/DOX and MCF7/DOX500 cells. Control experiments confirmed that examined compounds in these ranges of concentration did not affect the cell growth of MCF7/DOX and MCF7/DOX500 sublines (80-100% of control cell growth was observed in the presence of studied polyphenols).
2
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Low stimulation of NADH oxidation and oxygen consumption by 5-iminodaunorubicin and its derivatives

80%
Tarasiuk J., Stefańska B., Borowski E.
Acta Biochimica Polonica
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1990
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vol. 37
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issue 2
251-259
3
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The effect of new non-cross resistant antitumour agents on the energy state of human erythrocytes

61%
Nowak R., Baranowska-Bosiacka I., Stefańska B., Machaliński B., Hłyńczak A. J., Tarasiuk J.
Acta Biochimica Polonica
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2005
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vol. 52
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issue 4
953-957
EN
Multidrug resistance (MDR) of tumour cells is related to the overexpression of ATP-dependent pumps responsible for the active efflux of antitumour agents out of resistant cells. Benzoperimidine and anthrapyridone compounds exhibit comparable cytotoxic activity against sensitive and MDR tumour cells. They diffuse extremely rapidly across the plasma membrane and render the ATP-dependent efflux inefficient. Such uptake could disturb an energy metabolism of normal cells possessing an elevated level of ATP-dependent proteins, especially erythrocytes having a high level of the MRP1, MRP4 and MRP5 proteins. In this study the effect of five antitumour agents: benzoperimidine (BP1), anthrapyridones (CO1, CO7) and reference drugs used in the clinic: doxorubicin (DOX) and pirarubicin (PIRA), on the energetic state in human erythrocytes has been examined. These compounds have various types of structure and kinetics of cellular uptake (slow - DOX, CO7, moderate - PIRA, fast - BP1, CO1) resulting in their different ability to saturate ATP-dependent transporters. The energetic state of erythrocytes was examined by determination of purine nucleotide contents (ATP, ADP, AMP), NAD+ and values of adenylate energy charge (AEC) using an HPLC method. It was found that the level of nucleotides as well as the AEC value of erythrocytes were not changed during 24 h of incubation with these agents independently of their structure and ability to saturate ATP-dependent pumps. This is a very promising result in view of their potential use in the clinic as antitumour drugs against multidrug resistant cancers.
4
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The ability of new formamidine sugar-modified derivatives of daunorubicin to stimulate free radical formation in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase and xanthine oxidase

61%
Pawłowska J., Tarasiuk J., Borowski E., Wąsowska M., Oszczapowicz I., Roland Wolf C.
Acta Biochimica Polonica
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2000
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vol. 47
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issue 1
141-147
EN
Some sterically hindered N-substituted derivatives of daunorubicin are known to be poor substrates for NADH dehydrogenase, NADPH cytochrome P450 reductase and xanthine oxidase. In consequence, poor oxygen radical generation by these compounds is observed. In this study we examined a new family of sugar-N-substituted derivatives of daunorubicin bearing a bulky substituent introduced on the nitrogen atom through the amidine spacer. These compounds were found to be very active in radical formation catalyzed by all three studied enzymes. Thus, the introduction of a heterocyclic ring, even if it is bulky but flexible, on the nitrogen atom of daunosamine moiety through the one-atom spacer (amidine group), does not induce the steric hindrance effect on the interaction of daunorubicin derivatives with these flavoprotein enzymes.
5
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Molecular modeling of singlet-oxygen binding to anthraquinones in relation to the peroxidating activity of antitumor anthraquinone drugs

52%
Liwo A., Jeziorek D., Ossowski T., Dyl D., Tempczyk A., Tarasiuk J., Nowacka M., Borowski E., Woźnicki W.
Acta Biochimica Polonica
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1995
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vol. 42
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issue 4
445-456
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